Rituximab selectively suppresses specific islet antibodies.

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Yu, Liping; Herold, Kevan; Krause-Steinrauf, Heidi; McGee, Paula L; Bundy, Brian; Pugliese, Alberto; Krischer, Jeff; Eisenbarth, George S

2011-10-01

The TrialNet Study Group evaluated rituximab, a B-cell-depleting monoclonal antibody, for its effect in new-onset patients with type 1A diabetes. Rituximab decreased the loss of C-peptide over the first year of follow-up and markedly depleted B lymphocytes for 6 months after administration. This article analyzes the specific effect of rituximab on multiple islet autoantibodies. A total of 87 patients between the ages of 8 and 40 years received either rituximab or a placebo infusion weekly for four doses close to the onset of diabetes. Autoantibodies to insulin (IAAs), GAD65 (GADAs), insulinoma-associated protein 2 (IA2As), and ZnT8 (ZnT8As) were measured with radioimmunoassays. The primary outcome for this autoantibody analysis was the mean level of autoantibodies during follow-up. Rituximab markedly suppressed IAAs compared with the placebo injection but had a much smaller effect on GADAs, IA2As, and ZnT8As. A total of 40% (19 of 48) of rituximab-treated patients who were IAA positive became IAA negative versus 0 of 29 placebo-treated patients (P 1 year in insulin-treated patients. For the patients receiving insulin for >2 weeks prior to rituximab administration, we cannot assess whether rituximab not only blocks the acquisition of insulin antibodies induced by insulin administration and/or also suppresses preformed insulin autoantibodies. Studies in prediabetic non-insulin-treated patients will likely be needed to evaluate the specific effects of rituximab on levels of IAAs.

Efficacy of rituximab and plasmapharesis in an adult patient with antifactor H autoantibody-associated hemolytic uremic syndrome: A case report and literature review.

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Deville, Clemence; Garrouste, Cyril; Coppo, Paul; Evrard, Bertrand; Lautrette, Alexandre; Heng, Anne Elisabeth

2016-09-01

Antifactor H antibody (anti-CFHAb) is found in 6% to 25% cases of atypical hemolytic uremic syndrome (aHUS) in children, but has been only exceptionally reported in adults. There is no consensus about the best treatment for this type of aHUS. We report the case of an adult patient treated successfully with plasma exchange (PE), steroids, and rituximab.A 27-year-old Caucasian male presented to hospital with anemia, thrombocytopenia, and acute renal failure. One week earlier, he had digestive problems with diarrhea. The diagnosis of anti-CFHAb-associated aHUS (82,000 AU/mL) without CFHR gene mutations was established.He received Rituximab 375 mg/m (4 pulses) with PE and steroids. This treatment achieved renal and hematological remission at day (D) 31 and negative anti-CFHAb at D45 (<100 AU/mL). At D76, a fifth rituximab pulse was performed while CD19 was higher than 10/mm. Steroids were stopped at month (M) 9. The patient has not relapsed during long-term follow-up (M39).Rituximab therapy can be considered for anti-CFHAb-associated aHUS. Monitoring of anti-CFHAb titer may help to guide maintenance therapeutic strategies including Rituximab infusion.

Parvovirus B19 reactivation presenting as neutropenia after rituximab treatment.

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Klepfish, A; Rachmilevitch, E; Schattner, A

2006-11-01

A patient with primary biliary cirrhosis and associated refractory immune thrombocytopenic purpura was treated with 4 weekly courses of rituximab, a monoclonal antibody targeting B-cell surface antigen CD20. Her thrombocyte count and even cholestatic liver function tests improved. However, 17 weeks after rituximab treatment, she developed severe neutropenia (absolute neutrophil count 0.23x10(3)/mul) and recurrent thrombocytopenia with abnormal bone marrow of all three lineages. Although delayed-onset neutropenia has been reported after rituximab, reactivated viral infections have also been encountered. Parvovirus B19 was suspected and confirmed as the cause of neutropenia in our patient. The patient was supported by GCSF treatment and recovered uneventfully after several weeks. Neutropenia after rituximab can also be the predominant manifestation of reactivated parvovirus B19 infection and have a favorable prognosis.

Prespecified candidate biomarkers identify follicular lymphoma patients who achieved longer progression-free survival with bortezomib-rituximab versus rituximab.

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Coiffier, Bertrand; Li, Weimin; Henitz, Erin D; Karkera, Jayaprakash D; Favis, Reyna; Gaffney, Dana; Shapiro, Alice; Theocharous, Panteli; Elsayed, Yusri A; van de Velde, Helgi; Schaffer, Michael E; Osmanov, Evgenii A; Hong, Xiaonan; Scheliga, Adriana; Mayer, Jiri; Offner, Fritz; Rule, Simon; Teixeira, Adriana; Romejko-Jarosinska, Joanna; de Vos, Sven; Crump, Michael; Shpilberg, Ofer; Zinzani, Pier Luigi; Cakana, Andrew; Esseltine, Dixie-Lee; Mulligan, George; Ricci, Deborah

2013-05-01

Identify subgroups of patients with relapsed/refractory follicular lymphoma deriving substantial progression-free survival (PFS) benefit with bortezomib-rituximab versus rituximab in the phase III LYM-3001 study. A total of 676 patients were randomized to five 5-week cycles of bortezomib-rituximab or rituximab. The primary end point was PFS; this prespecified analysis of candidate protein biomarkers and genes was an exploratory objective. Archived tumor tissue and whole blood samples were collected at baseline. Immunohistochemistry and genetic analyses were completed for 4 proteins and 8 genes. In initial pairwise analyses, using individual single-nucleotide polymorphism genotypes, one biomarker pair (PSMB1 P11A C/G heterozygote, low CD68 expression) was associated with a significant PFS benefit with bortezomib-rituximab versus rituximab, controlling for multiple comparison corrections. The pair was analyzed under dominant, recessive, and additive genetic models, with significant association with PFS seen under the dominant model (G/G+C/G). In patients carrying this biomarker pair [PSMB1 P11A G allele, low CD68 expression (≤50 CD68-positive cells), population frequency: 43.6%], median PFS was 14.2 months with bortezomib-rituximab versus 9.1 months with rituximab (HR 0.47, P < 0.0001), and there was a significant overall survival benefit (HR 0.49, P = 0.0461). Response rates were higher and time to next antilymphoma therapy was longer in the bortezomib-rituximab group. In biomarker-negative patients, no significant efficacy differences were seen between treatment groups. Similar proportions of patients had high-risk features in the biomarker-positive and biomarker-negative subsets. Patients with PSMB1 P11A (G allele) and low CD68 expression seemed to have significantly longer PFS and greater clinical benefit with bortezomib-rituximab versus rituximab. ©2013 AACR.

Rituximab induced hypoglycemia in non-Hodgkin's lymphoma

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Lali V

2006-12-01

Full Text Available Abstract Background Hypoglycemia is a vary rare toxicity of rituximab. The exact mechanism of rituximab induced hypoglycemia is not clear. Case presentation A 50 year old female presented with a left tonsillar non Hodgkin's lymphoma and was started on R-CHOP chemotherapy. Twenty four hours after the first rituximab infusion, she developed hypoglycemia which was managed by IV glucose infusion. Conclusion Hypoglycemia following rituximab administration is rare. Possibilities of hypoglycemia should be kept in mind in patients developing symptoms like fatigue, restlessness, and sweating while on rituximab therapy.

Prolonged Remission in Neuromyelitis Optica Following Cessation of Rituximab Treatment.

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Weinfurtner, Kelley; Graves, Jennifer; Ness, Jayne; Krupp, Lauren; Milazzo, Maria; Waubant, Emmanuelle

2015-09-01

Neuromyelitis optica is an autoimmune disease characterized by acute episodes of transverse myelitis and optic neuritis. Several small, open-label studies suggest rituximab, a monoclonal antibody against CD20, prevents relapses in neuromyelitis optica; however, there is little consensus on timing or duration of treatment. Here we report four patients with severe relapsing neuromyelitis optica who were stabilized on rituximab and, after discontinuing treatment, continued to experience prolonged remission of their disease. Remission ranged from 4.5 to 10.5 years total, including 3 to 9 years off all therapies. The patients had sustained clinical responses despite normal B-lymphocyte levels and, in at least 2 patients, continued seropositivity for aquaporin-4 antibodies. These cases suggest that rituximab may induce prolonged remission in certain neuromyelitis optica patients, and they highlight the need for further elucidation of rituximab's mechanism in neuromyelitis optica. © The Author(s) 2014.

Progress in immunotherapy Rituximab

International Nuclear Information System (INIS)

El-Habbash, Manal M.; Alwindi, Abukris M.

2007-01-01

Rituximab is an anti-CD-20 chimeric monoclonal antibody that has shown substantial activity. Since its discovery, rituximab has been used with great success in a variety of hematological malignancies. Its success in the management of aggressive lymphomas led to expansion of its use in other conditions such as stem cell transplantation, post- transplant lymphoproliferative disorder, and other non-malignant conditions where B cell activation is thought to be important, such as idiopathic thrombocytopenic purpura and rheumatoid arthritis. The side effects have been remarkably few, particularly, infection is not more common that chemotherapy alone. This article reviews the structure, mechanism of action and uses of rituximab as monotherapy or in combination with chemotherapy. (author)

Single-dose Rituximab Therapy for Refractory Idiopathic Membranous Nephropathy: A Single-center Experience

OpenAIRE

Katsuno, Takayuki; Ozaki, Takenori; Kim, Hangsoo; Kato, Noritoshi; Suzuki, Yasuhiro; Akiyama, Shinichi; Ishimoto, Takuji; Kosugi, Tomoki; Tsuboi, Naotake; Ito, Yasuhiko; Maruyama, Shoichi

2017-01-01

To date, a recognized treatment for refractory membranous nephropathy (MN) has not been established. Recently, several reports have indicated the efficacy of rituximab as a novel treatment option. However, only a few published accounts exist of rituximab therapy for idiopathic MN (IMN) in the Asian population. We present the cases of three IMN patients who were treated with single-dose rituximab after they showed no response to conventional therapies, including corticosteroids, cyclosporine, ...

Discovery – Development of Rituximab

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NCI funded the development of rituximab, one of the first monoclonal antibody cancer treatments. With the discovery of rituximab, more than 70 percent of patients diagnosed with non-hodgkin lymphoma now live five years past their initial diagnosis.

Kinetics of Rituximab Excretion into Urine and Peritoneal Fluid in Two Patients with Nephrotic Syndrome.

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Stahl, Klaus; Duong, Michelle; Schwarz, Anke; Wagner, A D; Haller, Hermann; Schiffer, Mario; Jacobs, Roland

2017-01-01

Clinical observations suggest that treatment of Rituximab might be less effective in patients with nephrotic range proteinuria when compared to nonnephrotic patients. It is conceivable that the reason for this is that significant amounts of Rituximab might be lost in the urine in a nephrotic patient and that these patients require a repeated or higher dosage. However, this has not been systematically studied. In this case report we describe two different patients with nephrotic range proteinuria receiving Rituximab. The first patient received Rituximab for therapy resistant cryoglobulinemic membranoproliferative glomerulonephritis and the other for second line treatment of Felty's syndrome. We employed flow cytometry to determine the amount of Rituximab excretion in both urine and peritoneal fluid specimens in these patients following administration of Rituximab. We found that a significant amount of Rituximab is lost from the circulation by excretion into the urine. Furthermore we saw a close correlation of the excretion of Rituximab to the excretion of IgG molecules suggesting selectivity of proteinuria as the determining factor of Rituximab excretion. Further larger scale clinical studies could have the potential to evaluate an optimal cut-off value of IgG urinary loss before a possible administration of Rituximab therefore contributing to a more individualized treatment approach in patients with nonselective and nephrotic range proteinuria.

Achieving a satisfactory clinical and biochemical response in antiphospholipid syndrome and severe thrombocytopenia with rituximab: two case reports.

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Gamoudi, Donia; Cutajar, Melanie; Gamoudi, Nadia; Camilleri, David James; Gatt, Alex

2017-06-01

In AP syndrome (APS) with severe thrombocytopenia, rituximab represents a unique drug which can balance the effect of bleeding and thrombosis. By reducing the production of autoantibodies, rituximab can simultaneously raise the platelets and reduce the chance of thrombosis by suppressing APL antibodies. Rituximab can supersede splenectomy as second-line therapy in similar patients.

A case of "refractory" lupus erythematosus profundus responsive to rituximab [case report].

LENUS (Irish Health Repository)

McArdle, Adrian

2012-02-01

Lupus erythematosus profundus is a rare complication of systemic lupus erythematosus characterized by the presence of deep, tender subcutaneous nodules. A 22-year-old African-American female with extensive lupus profundus resistant to conventional therapies was treated with two infusions of the anti-CD20 monoclonal antibody, rituximab, at a dosage of 1,000 mg each. The patient demonstrated a remarkable clinical response as indicated by the disappearance of the nodules. B-cell depletion therapy with rituximab used alone or in combination with other therapies may be a viable option in patients with lupus profundus refractory to current therapies.

Rituximab in anti-GBM disease: A retrospective study of 8 patients.

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Touzot, Maxime; Poisson, Johanne; Faguer, Stanislas; Ribes, David; Cohen, Pascal; Geffray, Loic; Anguel, Nadia; François, Helene; Karras, Alexandre; Cacoub, Patrice; Durrbach, Antoine; Saadoun, David

2015-06-01

Anti-glomerular basement membrane (GBM) disease is a rare autoantibody-mediated disorder presenting as rapidly progressive glomerulonephritis, and often with pulmonary hemorrhage. Antibody removal with plasmapheresis and immunosuppressive drugs are the cornerstones of the treatment. Data regarding the use of specific B-cell depleting therapy such as rituximab are lacking. We conducted a retrospective observational study of 8 patients with severe and/or refractory GBM disease that received rituximab therapy. Eight patients (2 men, 6 women) with a mean age of 26 ± 13.1 years old were included. Seven had severe renal involvement [median creatinin level was 282 μmol/l, range (65-423)] requiring high immunosuppressive or plasmapheresis dependent, and two had relapse of pulmonary hemorrhage including one with renal failure. Patients received an initial immunosuppressive treatment including steroid and cyclosphosphamide (n = 8) and plasmapheresis (n = 5). Except one late relapse, rituximab therapy was started within two months after diagnosis. All patients except one received 4 weekly dose of rituximab (375 mg(2)). Anti-GBM antibodies were still present in 6/8 patients, at rituximab initiation. Complete remission was observed in 7 out of 8 patients, mostly 3 months after rituximab therapy. After a mean follow-up of 25.6 months (range 4-93), patient and renal survival were 100% and 75% respectively, but rituximab use did not improve GFR. Anti-GBM antibodies remained negative for all patients during follow-up. Only one patient developed a severe bacterial infection but no opportunistic or viral infections were reported. Rituximab may represent an additional and/or alternative therapy in the induction treatment of anti-GBM disease. Copyright © 2015 Elsevier Ltd. All rights reserved.

Kinetics of Rituximab Excretion into Urine and Peritoneal Fluid in Two Patients with Nephrotic Syndrome

Directory of Open Access Journals (Sweden)

Klaus Stahl

2017-01-01

Full Text Available Clinical observations suggest that treatment of Rituximab might be less effective in patients with nephrotic range proteinuria when compared to nonnephrotic patients. It is conceivable that the reason for this is that significant amounts of Rituximab might be lost in the urine in a nephrotic patient and that these patients require a repeated or higher dosage. However, this has not been systematically studied. In this case report we describe two different patients with nephrotic range proteinuria receiving Rituximab. The first patient received Rituximab for therapy resistant cryoglobulinemic membranoproliferative glomerulonephritis and the other for second line treatment of Felty’s syndrome. We employed flow cytometry to determine the amount of Rituximab excretion in both urine and peritoneal fluid specimens in these patients following administration of Rituximab. We found that a significant amount of Rituximab is lost from the circulation by excretion into the urine. Furthermore we saw a close correlation of the excretion of Rituximab to the excretion of IgG molecules suggesting selectivity of proteinuria as the determining factor of Rituximab excretion. Further larger scale clinical studies could have the potential to evaluate an optimal cut-off value of IgG urinary loss before a possible administration of Rituximab therefore contributing to a more individualized treatment approach in patients with nonselective and nephrotic range proteinuria.

Prophylaxis of hepatitis B reactivation using lamivudine in a patient receiving rituximab.

Science.gov (United States)

Hamaki, T; Kami, M; Kusumi, E; Ueyama, J; Miyakoshi, S; Morinaga, S; Mutou, Y

2001-12-01

A 53-year-old man who had a history of fluminant hepatitis caused by precore mutant hepatitis B virus (HBV) was admitted to our hospital for the treatment of relapsed non-Hodgkin's lymphoma in July 2000. At admission, serum levels of aspartate aminotransferase and alanine aminotransferase were normal, but he tested positive for HBs antigen. The titer was 64-fold by radioimmunoassay. We initiated lamivudine at a daily dose of 75 mg to prevent HBV proliferation during chemotherapy. By September 2000, he had received six courses of rituximab at 375 mg/m(2) and four courses of fludarabine and mitoxantrone. No hepatic damage was observed from the initiation of treatment until March 2001. At present, four months after the completion of chemotherapy, he continues lamivudine, and the titer of HBs antigen is low at 4-fold. Rituximab is usually associated with mild toxicity, usually limited to infusion periods. The drug is not generally associated with increased incidence of opportunistic infections. However, some case reports have been recently published on severe viral infections following administration of rituximab. These include fluminant hepatitis caused by HBV, pure red cell aplasia due to parvovirus B19 and fatal varicella-zoster infection. While it remains unknown whether rituximab can be safely administered in patients with chronic HBV infection, this case report suggested that prophylactic administration of lamivudine is beneficial for suppressing reactivation of HBV during chemotherapy including rituximab. Rituximab should be used cautiously for patients with HBV infection, but prophylactic administration of lamivudine may be beneficial for preventing reactivation of HBV. Copyright 2001 Wiley-Liss, Inc.

Effect of Rituximab in Patients With Leucine-Rich, Glioma-Inactivated 1 Antibody–Associated Encephalopathy

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Irani, Sarosh R.; Gelfand, Jeffrey M.; Bettcher, Brianne M.; Singhal, Neel S.; Geschwind, Michael D.

2015-01-01

IMPORTANCE This observational study describes the efficacy and safety of rituximab in 5 patients with voltage-gated potassium channel (VGKC)–complex/leucine-rich, glioma-inactivated 1 (LGI1) antibody–associated encephalopathy. Rituximab is a monoclonal antibody that targets CD20 and is used to treat other neurologic and nonneurologic diseases. OBSERVATIONS This case series reports sequential seizure frequencies, modified Rankin Scale scores, and VGKC-complex antibody titers in 5 adult patients (median age, 65 years; range, 48–73 years) treated with rituximab. Median time from symptom onset to rituximab initiation was 414 days (range, 312–851 days). One patient showed a rapid clinical improvement after treatment with rituximab alone and experienced a rituximab-responsive clinical relapse. Another showed possible improvement on neuropsychometric memory indexes after rituximab therapy. In contrast, all patients showed robust responses to treatment with glucocorticoids, intravenous immunoglobulins, and/or plasma exchange at some point in their illness. Treatment with glucocorticoids—less so with intravenous immunoglobulins and plasma exchange—was associated with the most marked reductions in VGKC-complex antibodies. The only patient who did not receive glucocorticoids showed the poorest clinical and serologic responses. CONCLUSIONS AND RELEVANCE Rituximab was well tolerated in this predominantly older adult patient population and may be an effective option for some patients with LGI1 antibody–associated encephalopathy. Glucocorticoid therapy appears particularly efficacious. Earlier rituximab administration and randomized trials are required to formally assess efficacy. PMID:24842754

Acute neurological worsening after Rituximab treatment in patients with anti-MAG neuropathy.

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Sala, Emilie; Robert-Varvat, Florence; Paul, Stéphane; Camdessanché, Jean-Philippe; Antoine, Jean-Christophe

2014-10-15

Patients with peripheral neuropathy and anti-MAG monoclonal IgM may respond to Rituximab, a humanized monoclonal anti-CD20 antibody. We report on three patients with peripheral neuropathy and anti-MAG monoclonal IgM who deteriorated under Rituximab and reviewed seven previously published cases. Worsening was acute and severe, and occurred during the treatment period. All the patients improved after deterioration but at final evaluation only one was improved comparatively to baseline, five were worsened and four were stabilized. Deterioration was not clearly associated with an increase of the anti-MAG antibody titer. Two patients received Rituximab prior or after the course which induced worsening without adverse reaction. Although rare, acute worsening of the neuropathy can occur after Rituximab. The deterioration is however reversible within some weeks to several months. Copyright © 2014 Elsevier B.V. All rights reserved.

Hepatitis B reactivation and rituximab: a new boxed warning and considerations for solid organ transplantation.

Science.gov (United States)

Martin, S T; Cardwell, S M; Nailor, M D; Gabardi, S

2014-04-01

Use of rituximab, a chimeric monoclonal antibody directed at the CD20 antigen, continues to increase in solid organ transplantation (SOT) for several off-label uses. In September 2013, the United States Food and Drug Administration (FDA) issued a Drug Safety Communication to oncology, rheumatology and pharmacy communities outlining a new Boxed Warning for rituximab. Citing 109 cases of fatal hepatitis B virus (HBV) reactivation in persons receiving rituximab therapy with previous or chronic HBV infection documented in their Adverse Event Reporting System (AERS), the FDA recommends screening for HBV serologies in all patients planned to receive rituximab and antiviral prophylaxis in any patient with a positive history of HBV infection. There is a lack of data pertaining to this topic in the SOT population despite an increase in off-label indications. Previous reports suggest patients receiving rituximab, on average, were administered six doses prior to HBV reactivation. Recommendations on prophylaxis, treatment and re-challenging patients with therapy after resolution of reactivation remain unclear. Based on data from the FDA AERS and multiple analyses in oncology, SOT providers utilizing rituximab should adhere to the FDA warnings and recommendations regarding HBV reactivation until further data are available in the SOT population. © Copyright 2014 The American Society of Transplantation and the American Society of Transplant Surgeons.

Study on the Preparation and Quality Control of 131I-Rituximab and 90Y-Rituximab for Non-Hodgkin-Lymphoma Therapy

International Nuclear Information System (INIS)

NguyenThi Thu; Duong Van Dong; Vo Thi Cam Hoa; Chu Van Khoa; Bui Van Cuong; Pham Ngoc Dien; Mai Phuoc Tho; Nguyen Thanh Binh; Dang Ho Hong Quang; Phan Quoc Thong; Mai Trong Khoa

2009-01-01

In recent years, radioimmunotherapy (RIT) has become a highly promising oncologic therapeutic modality with established clinically efficacy, particularly in the therapy of haematological malignancies. Rituximab, a chimeric monoclonal antibody targeted against the cluster designation (CD20) antigen was labelled with 131 I used in the treatment of B cell non Hodgkin's Lymphoma (NHL), B cell leukemia. In this study, the monoclonal antibody Rituximab was labelled with 131 I using chloramin T method (ChT). The optimized ChT concentration for the oxidation of 185 MBq of Na 131 I solution and 750□g of Rituximab was 20□g/20□l. The reaction time was 3 minutes at room temperature. The labeling reaction has stopped using sodiummetabisulphite (SMB). Labelling efficacy was controlled by ITLC. The reaction mixture was purified through the Sephadex G-25 PD10 Pharmacia column. The collected 131 I-Rituximab was filtered through a 0.20'm milipore sterile filter. The radiochemical labeling yield was more than 95%. Radiochemical purity of the radiopharmaceutical after purification was more than 99%. The product has been passed the test for sterility, bacterial endotoxins, to be sufficiency invivo and invitro stable and stability after labeling. 131 I-Rituximab was used for radioimmunoscintigraphy biodistribution in clinical. Rituximab was bound to the DTPA chelating agent using Hnatowich methods. Cyclic anhydride DTPA (cDTPAa, 0.1 mg/ml) was dissolved in chloroform and was degassed under a stream of nitrogen for 30 min. Rituximab solution in 0.05M bicarbonate buffer was immediately added and mixed for one minute at room temperature. The antibody Rituximab at different concentration (5mg/ml and 10mg/ml) was coupled with the cyclic DTPA anhydride, at molar ratios (cDTPAa : Rituximab) of 1:1, 3:1, 5:1, 10:1 and 20:1. The conjugation DTPA-Rituximab mixture was labelled with Y- 90 and purified and determinate of coupling efficiency. Coupling efficiency of cDTPA - to - Rituximab molar

Pneumocystis jiroveci Pneumonia in Patients with Non-Hodgkin's Lymphoma Receiving Chemotherapy Containing Rituximab

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Hung Chang

2008-11-01

Full Text Available Rituximab enhances treatment efficacy of B-lineage lymphoma by targeting CD20+ B-cells. Such target therapies may compromise the immune system and render patients susceptible to opportunistic infections. We report 2 cases of lymphoma complicated with Pneumocystis jiroveci (previously known as P. carinii pneumonia (PCP while being treated with rituximab-containing chemotherapy regimens. In both cases, PCP developed during the neutropenic period. With timely diagnosis and proper management, both were treated successfully. We searched the literature and found that such opportunistic infection occurred only infrequently in lymphoma patients, and it has not been reported in the large-scale clinical trials of rituximab. Such cases demonstrate the importance of taking PCP into diagnostic consideration in lymphoma patients receiving similar therapies.

Sequential rituximab and omalizumab for the treatment of eosinophilic granulomatosis with polyangiitis (Churg-Strauss syndrome).

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Aguirre-Valencia, David; Posso-Osorio, Iván; Bravo, Juan-Carlos; Bonilla-Abadía, Fabio; Tobón, Gabriel J; Cañas, Carlos A

2017-09-01

Eosinophilic granulomatosis with polyangiitis (EGPA), formerly known as Churg-Strauss syndrome (CSS), is a small vessel vasculitis associated with eosinophilia and asthma. Clinical manifestations commonly seen in patients presenting with EGPA range from upper airway and lung involvement to neurological, cardiac, cutaneous, and renal manifestations. Treatment for severe presentations includes steroids, cyclophosphamide, plasmapheresis, and recently, rituximab. Rituximab is associated with a good response in the treatment of vasculitis, but a variable response for the control of allergic symptoms. Here, we report a 16-year-old female patient with severe EGPA (gastrointestinal and cutaneous vasculitis, rhinitis and asthma) refractory to conventional treatment. She was treated with rituximab, which enabled rapid control of the vasculitis component of the disease, but there was no response to rhinitis and asthma. Additionally, she developed severe bronchospasm during rituximab infusion. Sequential rituximab and omalizumab were initiated, leading to remission of all manifestations of vasculitis, rhinitis, and asthma, in addition to bronchospasm related to rituximab infusion.

Rituximab as a first-line agent for the treatment of dermatomyositis.

LENUS (Irish Health Repository)

2012-02-01

B cells may play a pivotal role in the pathophysiology of DM, and reports have claimed that targeting B cells is a viable treatment option in patients with dermatomyositis. A 20-year-old girl presented in October 2007, with few weeks\\' history of proximal muscle weakness. Gottron\\'s papules were noted on her knuckles. She had normal inflammatory markers and negative autoantibody screen. Her CPK was 7,000 U\\/L (normal range 0-170) with an LDH of 1,300 U\\/L (normal range 266-500). EMG and muscle biopsy was consistent with active myositis. She had normal pulmonary function tests. HRCT showed no interstitial lung disease. She was started with 60 mg glucocorticoids (1 mg\\/kg), with a good clinical response. However, any attempt to taper down the steroid dose led to recurrence of her symptoms. The options of available immunosuppressive therapies, including the experimental usage of rituximab, were discussed with her; averse to long-term systemic treatments, she opted to try a course of rituximab. She had rituximab 1,000 mg on days 0 and 14, and her glucocorticoids were tapered in next few weeks. Now, 24 months since her rituximab infusions, she remains in complete clinical and biochemical remission and is naive to other immunosuppressive agents apart from glucocorticoids and rituximab. Depleting peripheral B cells with rituximab (one course) in our patient has led not only to complete resolution of muscle and skin disease (induction) but also remains off all immunosuppressives including glucocorticoids.

The Role of Rituximab in Lymphomas O papel do Rituximab nos linfomas

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Bertrand Coiffier

2002-01-01

Full Text Available Over the last years the treatment of non-Hodgkin's lymphoma underwent a great advance in relation to the diagnosis, classification, high-dose chemotherapy, and hematopoietic stem cell transplantation. Simultaneously with this, there was the development of new drugs and support therapy which enabled an improvement in the evolution and survival of the patients. The use of monoclonal antibodies against cancer cells is an old idea and in this report the results of the role of the anti-CD20-Rituximab in lymphomas is discussed.Nos últimos anos o tratamento do linfomas não Hodgkin apresentou um grande avanço no diagnóstico, classificação, quimioterapia com altas doses e o transplante de células percursoras hematopoiéticas. Simultaneamente houve o desenvolvimento de novas drogas e no tratamento de suporte o que possibilita um avanço na evolução e sobrevida dos pacientes. A idéia do emprego de anticorpos monoclonais no tratamento do câncer é antiga e neste relato são apresentados os resultados e o papel do anti-CD20-Rituximab nos linfomas.

Preparation & in vitro evaluation of 90Y-DOTA-rituximab

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Kameswaran, Mythili; Pandey, Usha; Dash, Ashutosh; Samuel, Grace; Venkatesh, Meera

2016-01-01

Background & objectives: Radioimmunotherapy is extensively being used for the treatment of non-Hodgkin's lymphoma (NHL). Use of rituximab, a chimeric anti-CD20 antibody directed against the CD20 antigen in combination with suitable beta emitters is expected to result in good treatment response by its cross-fire and bystander effects. The present work involves the conjugation of p-isothiocyanatobenzyl DOTA (p-SCN-Bn-DOTA) to rituximab, its radiolabelling with 90Y and in vitro and in vivo evaluation to determine its potential as a radioimmunotherapeutic agent. Methods: Rituximab was conjugated with p-SCN-Bn-DOTA at 1:1 antibody: DOTA molar ratio. The number of DOTA molecules linked to one molecule of rituximab was determined by radioassay and spectroscopic assay. Radiolabelling of rituximab with 90Y was carried out and its in vitro stability was evaluated. In vitro cell binding studies were carried out in Raji cells expressing CD20 antigen. Biodistribution studies were carried out in normal Swiss mice. Results: Using both radioassay and spectroscopic method, it was determined that about five molecules of DOTA were linked to rituximab. Radiolabelling of the rituximab conjugate with 90Y and subsequent purification on PD-10 column gave a product with radiochemical purity (RCP) > 98 per cent which was retained at > 90 per cent up to 72 h when stored at 37°C. In vitro cell binding experiments of 90Y-DOTA-rituximab with Raji cells exhibited specific binding of 20.7 ± 0.1 per cent with 90Y-DOTA-rituximab which reduced to 15.5 ± 0.2 per cent when incubated with cold rituximab. The equilibrium constant Kd for 90Y-DOTA-Rituximab was determined to be 3.38 nM. Radiolabelled antibody showed clearance via hepatobiliary and renal routes and activity in tibia was found to be quite low indicating in vivo stability of 90Y-DOTA-rituximab. Interpretation & conclusions: p-SCN-Bn-DOTA was conjugated with rituximab and radiolabelling with 90Y was carried out. In vitro studies carried

[Castleman's disease: Rapid desensitization for hypersensitivity reaction to rituximab].

Science.gov (United States)

Boin, C; Lambert, S; Thomann, P; Aujoulat, O; Kieffer, P

2016-06-01

Rapid desensitization allows secure administration of a drug and is indicated when there is no therapeutic alternative. We report a 49-year-old patient who presented with a hypersensitivity reaction following an infusion of rituximab (375mg/m(2)) in the context of a Castleman's syndrome. After a clinical flare (splenomegaly, adenopathies) despite treatment with tocilizumab, anakinra and valganciclovir, the reintroduction of rituximab was decided, according to the rapid desensitization protocol. Four full dose desensitizations were successfully performed allowing immediate clinical improvement (apyrexia, loss of sweating and lymphadenopathy, splenomegaly partial regression) and biological (negativation of HHV8 viral load, and disappearance of neutropenia, anemia and thrombocytopenia). Rapid desensitization is a promising method for the pursuit of rituximab therapy after a hypersensitivity reaction and should be considered in patients with no acceptable therapeutic alternative. Copyright © 2015 Société Nationale Française de Médecine Interne (SNFMI). Published by Elsevier SAS. All rights reserved.

Rituximab for nephrotic syndrome in children.

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Iijima, Kazumoto; Sako, Mayumi; Nozu, Kandai

2017-04-01

Idiopathic nephrotic syndrome is the most common chronic glomerular disease in children. At least 20 % of children with this syndrome show frequent relapses and/or steroid dependence during or after immunosuppressive therapies, a condition defined as complicated frequently relapsing/steroid-dependent nephrotic syndrome (FRNS/SDNS). Approximately 1-3 % of children with idiopathic nephrotic syndrome are resistant to steroids and all immunosuppressive agents, a condition defined as refractory steroid-resistant nephrotic syndrome (SRNS); these SRNS children have a high risk of end-stage renal failure. Rituximab, a chimeric anti-CD20 monoclonal antibody, has been shown to be effective for patients with complicated FRNS/SDNS and refractory SRNS. This review describes the recent results of rituximab treatment applied to pediatric nephrotic syndrome, as well as those of our recent study, a multicenter, double-blind, randomized, placebo-controlled trial of rituximab for childhood-onset complicated FRNS/SDNS (RCRNS01). The overall efficacy and safety of rituximab for this disease are discussed.

Desensitization to rituximab in a multidisciplinary setting.

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Amorós-Reboredo, Patrícia; Sánchez-López, Jaime; Bastida-Fernández, Carla; do Pazo-Oubiña, Fernando; Borràs-Maixenchs, Núria; Giné, Eva; Valero, Antonio; Creus-Baró, Natàlia

2015-10-01

The need to offer first-line therapy to the increasing number of patients who have suffered an hypersensitivity reaction has stimulated the use of rapid desensitization protocols. To present our experience working as a multidisciplinary team using a rituximab rapid desensitization scheme. Patient demographics, allergic reaction, skin tests to rituximab, number of desensitizations, reactions during the desensitization protocol and actions taken, number of administered and completed cycles, were retrospectively collected in patients who received at least one desensitization to rituximab. Number of desensitizations successfully managed. Between 2012 and June 2013 five patients received a total of 19 desensitizations to rituximab using a 12 step rapid desensitization protocol. All patients received the scheduled chemotherapeutic cycles as inpatients, with no delay in administration dates. Three patients presented a hypersensitivity reaction during the first desensitization and in one patient the event occurred again during the second treatment cycle. All reactions occurred in the last step, when the infusion rate reached the maximum speed. The developed protocol for rapid desensitization was successful in five patients receiving rituximab. Patients could receive the full intended dose.

Rituximab in the treatment of shrinking lung syndrome in systemic lupus erythematosus.

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Peñacoba Toribio, Patricia; Córica Albani, María Emilia; Mayos Pérez, Mercedes; Rodríguez de la Serna, Arturo

2014-01-01

Shrinking lung syndrome (SLS) is a rare manifestation of systemic lupus erythematosus. We report the case of a patient with non-responding SLS (neither to glucocorticoids nor immunosupresors), who showed remarkable improvement after the onset of treatment with rituximab. Although there is a little evidence, treatment with rituximab could be proposed in SLS when classical treatment fails. Copyright © 2013 Elsevier España, S.L. All rights reserved.

Clinical evaluation of rituximab treatment for neuromyelitis optica.

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Fernández-Megía, M J; Casanova-Estruch, B; Pérez-Miralles, F; Ruiz-Ramos, J; Alcalá-Vicente, C; Poveda-Andrés, J L

2015-10-01

Neuromyelitis optica is an inflammatory and usually relapsing demyelinating autoimmune disease of the central nervous system that targets the optic nerves and spinal cord. Rituximab has been used for different neurological diseases that are probably immune-mediated or involving humoural immunity. The objective of this study is to evaluate the efficacy and safety of rituximab as treatment for neuromyelitis optica in a tertiary hospital. Retrospective study of patients with neuromyelitis optica treated with rituximab 1000mg on days 1 and 15, repeated every 6 to 8 months. We recorded EDSS score, relapse rate, overall condition, CD19+ count, presence of anti-NMO antibodies, and possible adverse reactions. Six patients were treated; all were women with a median age of 46 years (range, 38-58). Anti-NMO antibodies were detected in 3 patients (50%). Baseline EDSS was 4 (range 2.0-5.5). Two patients had previously been treated with an immunomodulatory drug. Median time from the first rituximab infusion to first relapse was 3.7 years (range 1.7-6.9). Two patients had infusion reactions after the first dose of rituximab. Four patients remained relapse-free and their EDSS score did not progress during rituximab treatment, one patient showed no clinical improvement, and one patient could not be evaluated. Rituximab can be considered an attractive therapeutic alternative for patients with neuromyelitis optica as there are no approved treatments for this disease. Further studies with rituximab are needed to establish the role of this drug in treating neuromyelitis optica. Copyright © 2013 Sociedad Española de Neurología. Published by Elsevier España, S.L.U. All rights reserved.

Detection and quantification of rituximab in the human urine.

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Jacobs, Roland; Langer-Jacobus, Thais; Duong, Michelle; Stahl, Klaus; Haller, Hermann; Schmidt, Reinhold E; Schiffer, Mario

2017-12-01

B cell depletion by rituximab treatment might be inefficient in patients suffering from nephrotic syndrome. Due to the impaired glomerular filtration barrier a significant portion of the therapeutic antibody might be lost into the urinary space. In order to determine the amount of rituximab in the urine of such patients, CD20+ Daudi cells were stained with the patients' urine followed by a fluorochrome-labeled secondary antibody. Mean fluorescence intensity of that way labeled Daudi cells was determined by flow cytometry. Control samples with defined rituximab concentrations were used to create standard curves. The analyses revealed that all nephelometric IgG+ urine samples tested also manifested rituximab at concentrations between 100 and 46,707μg/L. The flow cytometry-based approach is an easy and reliable method to assess rituximab in patients' urine samples for monitoring individual rituximab treatment courses in all patients co-presenting impaired renal filtration. Presence of such antibodies in the urine could be considered as criteria to modify the formulation or modality of rituximab delivery in order to prevent the loss of the therapeutic antibodies and thereby ensuring efficacy of the therapy. Copyright © 2017 Elsevier B.V. All rights reserved.

Successful pregnancy after rituximab in a women with recurrent in vitro fertilisation failures and anti-phospholipid antibody positive.

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Ng, C T

2012-02-01

We report a case of successful pregnancy after rituximab in a patient with a history of in vitro fertilisation (IVF) failures and positive anti-cardiolipin antibody (ACA). Following a course of rituximab, her ACA became negative and she successfully conceived with IVF treatment. This is the first case in literature describing the use of rituximab therapy in this clinical scenario.

Preparation & in vitro evaluation of ⁹⁰Y-DOTA-rituximab.

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Kameswaran, Mythili; Pandey, Usha; Dash, Ashutosh; Samuel, Grace; Venkatesh, Meera

2016-01-01

Radioimmunotherapy is extensively being used for the treatment of non-Hodgkin's lymphoma (NHL). Use of rituximab, a chimeric anti-CD20 antibody directed against the CD20 antigen in combination with suitable beta emitters is expected to result in good treatment response by its cross-fire and bystander effects. The present work involves the conjugation of p-isothiocyanatobenzyl DOTA (p-SCN-Bn-DOTA) to rituximab, its radiolabelling with [90] Y and in vitro and in vivo evaluation to determine its potential as a radioimmunotherapeutic agent. Rituximab was conjugated with p-SCN-Bn-DOTA at 1:1 antibody: DOTA molar ratio. The number of DOTA molecules linked to one molecule of rituximab was determined by radioassay and spectroscopic assay. Radiolabelling of rituximab with 90 Y was carried out and its in vitro stability was evaluated. In vitro cell binding studies were carried out in Raji cells expressing CD20 antigen. Biodistribution studies were carried out in normal Swiss mice. Using both radioassay and spectroscopic method, it was determined that about five molecules of DOTA were linked to rituximab. Radiolabelling of the rituximab conjugate with [90] Y and subsequent purification on PD-10 column gave a product with radiochemical purity (RCP) > 98 per cent which was retained at > 90 per cent up to 72 h when stored at 37°C. In vitro cell binding experiments of 90 Y-DOTA-rituximab with Raji cells exhibited specific binding of 20.7 ± 0.1 per cent with [90] Y-DOTA-rituximab which reduced to 15.5 ± 0.2 per cent when incubated with cold rituximab. The equilibrium constant K d for 90 Y-DOTA-Rituximab was determined to be 3.38 nM. Radiolabelled antibody showed clearance via hepatobiliary and renal routes and activity in tibia was found to be quite low indicating in vivo stability of [90] Y-DOTA-rituximab. p-SCN-Bn-DOTA was conjugated with rituximab and radiolabelling with 90 Y was carried out. In vitro studies carried out in Raji cells showed the specificity of the

Successful Treatment of a Bullous Pemphigoid Patient with Rituximab Who Was Refractory to Corticosteroid and Omalizumab Treatments

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Aslı Bilgiç Temel

2017-02-01

Full Text Available Omalizumab is a humanized monoclonal antibody which is an FDA-approved treatment of severe allergic asthma and inhibits IgE binding to FcεRI. According to increasing evidence of IgE inhibition, omalizumab was suggested as a therapeutic approach for bullous pemphigoid (BP. Rituximab has been reported to be effective in various autoimmune diseases, including autoimmune bullous dermatoses. A specific protocol for the use of rituximab to treat BP patients is not yet available. There are only small case series and case reports about the efficacy and safety of rituximab in BP. Here we present a young BP patient who responded well to rituximab therapy and was refractory to conventional and omalizumab therapies although he had elevated IgE levels and eosinophilia. Our case supports the knowledge about the effectiveness and safety of rituximab not only in pemphigus but also in BP. On the other hand, although it did not work in our case, omalizumab may be a potentially effective agent in some carefully selected patients with certain subtypes of BP.

Time Savings with Rituximab Subcutaneous Injection versus Rituximab Intravenous Infusion: A Time and Motion Study in Eight Countries

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De Cock, Erwin; Kritikou, Persefoni; Sandoval, Mariana; Tao, Sunning; Wiesner, Christof; Carella, Angelo Michele; Ngoh, Charles; Waterboer, Tim

2016-01-01

Background Rituximab is a standard treatment for non-Hodgkin lymphoma. The SABRINA trial (NCT01200758) showed that a subcutaneous (SC) rituximab formulation did not compromise efficacy or safety compared with intravenous (IV) infusion. We aimed to quantify active healthcare professional (HCP) time and patient chair time for rituximab SC and IV, including potential time savings. Methods This non-interventional time and motion study was run in eight countries and 30 day oncology units. Rituximab SC data were collected alongside the MabCute trial (NCT01461928); IV data were collected per routine real-world practice. Trained observers recorded active HCP time for pre-specified tasks (stopwatch) and chair time (time of day). A random intercept model was used to analyze active HCP time (by task and for all tasks combined) in the treatment room and drug preparation area, drug administration duration, chair time and patient treatment room time by country and/or across countries. Active HCP and chair time were extrapolated to a patient’s first year of treatment (11 rituximab sessions). Results Mean active HCP time was 35.0 and 23.7 minutes for IV and SC process, respectively (-32%, p time was 27–58%. Absolute reduction in extrapolated active HCP time (first year of treatment) was 1.1–5.2 hours. Mean chair time was 262.1 minutes for IV, including 180.9 minutes infusion duration, vs. 67.3 minutes for SC, including 8.3 minutes SC injection administration (-74%, p time for the first year of treatment was 3.1–5.5 eight-hour days. Conclusions Compared with rituximab IV, rituximab SC was associated with reduced chair time and active HCP time. The latter could be invested in other activities, whereas the former may lead to more available appointments, reducing waiting lists and increasing the efficiency of day oncology units. Trial Registration ClinicalTrials.gov NCT01200758 PMID:27362533

Early plasmapheresis and rituximab for acute humoral rejection after ABO-compatible liver transplantation

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Nassim Kamar; Laurence Lavayssière; Fabrice Muscari; Janick Selves; Céline Guilbeau-Frugier; Isabelle Cardeau; Laure Esposito; Olivier Cointault; Marie Béatrice Nogier; Jean Marie Peron; Philippe Otal; Marylise Fort; Lionel Rostaing

2009-01-01

Acute humoral rejection (AHR) is uncommon after ABOcompatible liver transplantation. Herein, we report two cases of AHR treated with plasmapheresis and rituximab in two ABO-compatible liver-transplant patients with preformed anti-human leukocyte antigen donor-specific antibodies. Patient 1 experienced a biopsy-proven AHR at day 10 post-transplant. She was treated by steroid pulses, and OKT3. Because of persisting signs of biopsy-proven AHR at day 26, she was treated by plasmapheresis and rituximab. Liver enzyme levels did not improve, and she died on day 41. Patient 2 experienced a biopsy-proven AHR on day 10 post-transplant. She was treated by steroid pulses, plasmapheresis, and rituximab.Liver enzymes returned to within normal range 18 dafter diagnosis. Liver biopsies, at 3 and 9 mo post-transplant,showed complete resolution of AHR. We conclude that plasmapheresis should be started as soon as AHR is diagnosed, and be associated with a B-cell depleting agent. Rituximab may be considered as a first-line therapy.

A Case of Rituximab-Induced Necrotizing Fasciitis and a Review of the Literature

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Abdullateef Abdulkareem

2017-01-01

Full Text Available Necrotizing fasciitis is a fulminant soft tissue infection characterized by rapid progression and high mortality. Rituximab is a generally well-tolerated immunosuppresive medication used for B-cell malignancies and some rheumatological disorders. We report a case of a 69-year-old male with chronic lymphocytic leukemia who suffered necrotizing fasciitis of his left lower extremity secondary to Clostridium septicum 7 weeks after treatment with rituximab. Despite immediate intravenous antimicrobial therapy and emergent fasciotomy with extensive debridement, his hospital course was complicated by septic shock and he required an above-the-knee amputation. Physicians need to be aware of the possibility of necrotizing fasciitis in patients presenting with skin infections after rituximab therapy.

A Case of Rituximab-Induced Necrotizing Fasciitis and a Review of the Literature.

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Abdulkareem, Abdullateef; D'Souza, Ryan S; Shogbesan, Oluwaseun; Donato, Anthony

2017-01-01

Necrotizing fasciitis is a fulminant soft tissue infection characterized by rapid progression and high mortality. Rituximab is a generally well-tolerated immunosuppresive medication used for B-cell malignancies and some rheumatological disorders. We report a case of a 69-year-old male with chronic lymphocytic leukemia who suffered necrotizing fasciitis of his left lower extremity secondary to Clostridium septicum 7 weeks after treatment with rituximab. Despite immediate intravenous antimicrobial therapy and emergent fasciotomy with extensive debridement, his hospital course was complicated by septic shock and he required an above-the-knee amputation. Physicians need to be aware of the possibility of necrotizing fasciitis in patients presenting with skin infections after rituximab therapy.

A Case of Rituximab-Induced Necrotizing Fasciitis and a Review of the Literature

OpenAIRE

Abdulkareem, Abdullateef; D’Souza, Ryan S.; Shogbesan, Oluwaseun; Donato, Anthony

2017-01-01

Necrotizing fasciitis is a fulminant soft tissue infection characterized by rapid progression and high mortality. Rituximab is a generally well-tolerated immunosuppresive medication used for B-cell malignancies and some rheumatological disorders. We report a case of a 69-year-old male with chronic lymphocytic leukemia who suffered necrotizing fasciitis of his left lower extremity secondary to Clostridium septicum 7 weeks after treatment with rituximab. Despite immediate intravenous antimicrob...

Immunotherapy with rituximab in follicular lymphomas.

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Saguna, Carmen; Mut, Ileana Delia; Lupu, Anca Roxana; Tevet, Mihaela; Bumbea, Horia; Dragan, Cornel

2011-04-01

Non-Hodgkin Lymphomas (NHL) represent a recent and fascinating domain of hemato-oncology, in which remarkable progress has been made. The conventional treatments of indolent lymphomas do not extend the survival rate, nor do they cure. Recent directions are centered on using several new drugs that are capable of overcoming the mechanisms that are resistant to recovery. The initiation of immunotherapy (Rituximab in 1997) seems to have changed the natural evolution of follicular lymphomas (FL). It is possible that resistance to healing in follicular lymphomas may be neutralized with Rituximab by suppressing STAT-1 positive macrophages that are present in the cellular microenvironment.Thereinafter, the re-evaluation of recent models of prognostic and therapeutic paradigmas that were used in FL became compulsory.The purpose of the paper is to compare the evolution of patients with follicular lymphoma and the period of response, according to the treatments. The study group consisted of the 71 patients diagnosed with follicular lymphoma, out of a total of 767 malignant lymphatic proliferations with B cells, for a period of 7 years (2002-2008), at the Hematology Department, Hospital Coltea, Bucharest and Hematology Department, Universitary Hospital, BucharestResults and conclusions: Combining chemotherapy with Rituximab had better results compared to the same chemotherapy, administered alone, both in induction and in case of relapse. The overall response rate in our study group was 74.7%, out of which 42.3% complete remissions. The overall response rate was 84.61% in the Rituximab group, compared to 68.88% in patients without Rituximab.

Rituximab in treatment of idiopathic glomerulopathy

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Kamel El-Reshaid

2012-01-01

Full Text Available The aim of our study was to assess the role of rituximab (Mabthera in the treatment of patients with corticosteroid-resistant and calcineurin-inhibitors ± cellcept refractory idiopathic nephrotic syndrome (INS. A total of 83 patients who had required the previous treatment for a minimum of two years were included in the study. Our protocol included the use of rituximab in four-weekly slow infusions. Five patients were excluded as they could not tolerate rituximab infusion for allergic reaction. As expected, none of the patients had a decline in the total circulating lymphocyte counts yet all had achieved decline of their initially normal CD20 to < 0.5% one month after infusion. The decline persisted for eight to ten months later. In the minimal change disease (MCD group, 31 of the 32 patients had complete remission (CR and were off any immunosuppressive therapy and one of the previous non-responders (NR did not respond. Excluding two patients who had required retreatment, the others remained in CR (17 up to 28 months and six up to 36 months. Treatment with rituximab resulted in amelioration of NS in 17 of the 18 patients with focal segmental glomerulosclerosis (FSGS, while only one patient remained NR. Although renal function remained stable, proteinuria reappeared by eight to 12 months. Retreatment with rituximab resulted in a similar response with stable kidney function. In the 28 patients with membranous glomerulopathy (MG, 24 had achieved CR. Two patients failed to respond and two had partial remission. By 12 months, all patients relapsed. The response was within one month following treatment in patient with MCD, but was gradual within three months in FSGS and MG. Relapsers in all groups responded in a similar pattern to repeat dosing with the drug subsequently. Our prospective study represents an adequate number of patients with biopsy-proven subgroups of INS in both children and adults with long-term follow-up of treatment with rituximab

B Cell Depletion: Rituximab in Glomerular Disease and Transplantation

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S. Marinaki

2013-12-01

Full Text Available B cells play a central role in the pathogenesis of many autoimmune diseases. Selective targeting can be achieved with the use of the monoclonal antibody rituximab. In addition to being a drug for non-Hodgkin's lymphoma, rituximab is also an FDA-approved treatment for refractory rheumatoid arthritis and, since recently, ANCA vasculitis. It has shown efficacy in many autoimmune diseases. This review will discuss current evidence and the rationale of the use of rituximab in glomerular diseases, including randomized controlled trials. The focus will be on the use of rituximab in idiopathic membranous nephropathy, systemic lupus erythematosus and ANCA-associated vasculitis. The emerging role of rituximab in renal transplantation, where it seems to be important for the desensitization protocols for highly sensitized patients as well as for the preconditioning of ABO-incompatible recipients and the treatment of antibody-mediated rejection, will also be addressed.

Rituximab therapy in steroid-resistant severe hypothyroid Grave′s ophthalmopathy

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Aditi Pandit

2013-01-01

Full Text Available Association of Grave′s ophthalmopathy with hyperthyroidism is well known, and it has also been reported in euthyroid or hypothyroid autoimmune thyroiditis, which rarely requires treatment. Here, we report a case of bilaterally symmetrical severe corticosteroid-resistant hypothyroid Grave′s ophthalmopathy successfully treated with rituximab.

A retrospective study on the management of patients with rituximab refractory follicular lymphoma.

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Solal-Céligny, Philippe; Leconte, Pierre; Bardet, Aurélie; Hernandez, Juana; Troussard, Xavier

2018-01-01

Given that there are currently no clear recommendations regarding therapeutic options for rituximab refractory/relapsed follicular lymphoma patients, this study aimed to describe the real-life management of patients with refractory follicular lymphoma after systemic rituximab-containing regimens (rFL), and rFL patient characteristics. In this retrospective, national, multicentre study, descriptive analyses were mainly performed according to rituximab-containing regimen at rFL diagnosis [rituximab monotherapy (R-MONO), rituximab + chemotherapy (R-COMBO), and ongoing rituximab maintenance (R-MAINTAIN)]. The 459 analysed patients experienced rituximab-refractoriness between October 2013 and September 2015: R-MONO: 58 (13%), R-COMBO: 197 (43%), R-MAINTAIN: 204 (44%). Post-refractoriness strategies were heterogeneous: idelalisib ± rituximab (22%), without anti-lymphoma treatment (21%), rituximab-chemotherapy (21%) and stem cell transplantation (18%). Rituximab was continued in combination in 41% of cases. Chosen strategies varied according to patient age (without anti-lymphoma treatment: 28% of patients if ≥65 years vs. 12% if management and for the design of clinical trials in these patients. © 2017 John Wiley & Sons Ltd.

Rituximab and chemotherapy in diffuse large B-cell lymphoma.

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Sonet, Anne; Bosly, André

2009-06-01

Rituximab is an anti-CD20 chimeric monoclonal antibody with activity in nearly all subtypes of B-cell lymphomas. Association of rituximab with chemotherapy (mostly the cyclophosphamide, doxorubicin, vincristine and prednisolone [CHOP] regimen) in diffuse large B-cell lymphoma (DLBCL) represents an extraordinary revolution in the prognosis of DLBCL, and is the new standard of therapy in elderly and young, low-risk patients. Despite the lack of randomized, clinical trials in younger patients with high risk, rituximab is also a standard of care in these patients in clinical practice, at least in North America. The practice is based on observational trials (e.g., the British Columbia Registry) and the missing logic in classifying patients as 'younger' or 'older': 60 years old or 65 years old. In Europe, trials are ongoing to establish the best treatment for young, high-risk patients. Association of rituximab and chemotherapy deeply modifies prognostic factors defined before the rituximab era.

Efficacy of rituximab and plasmapharesis in an adult patient with antifactor H autoantibody-associated hemolytic uremic syndrome

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Deville, Clemence; Garrouste, Cyril; Coppo, Paul; Evrard, Bertrand; Lautrette, Alexandre; Heng, Anne Elisabeth

2016-01-01

Abstract Antifactor H antibody (anti-CFHAb) is found in 6% to 25% cases of atypical hemolytic uremic syndrome (aHUS) in children, but has been only exceptionally reported in adults. There is no consensus about the best treatment for this type of aHUS. We report the case of an adult patient treated successfully with plasma exchange (PE), steroids, and rituximab. A 27-year-old Caucasian male presented to hospital with anemia, thrombocytopenia, and acute renal failure. One week earlier, he had digestive problems with diarrhea. The diagnosis of anti-CFHAb-associated aHUS (82,000 AU/mL) without CFHR gene mutations was established. He received Rituximab 375 mg/m2 (4 pulses) with PE and steroids. This treatment achieved renal and hematological remission at day (D) 31 and negative anti-CFHAb at D45 (<100 AU/mL). At D76, a fifth rituximab pulse was performed while CD19 was higher than 10/mm3. Steroids were stopped at month (M) 9. The patient has not relapsed during long-term follow-up (M39). Rituximab therapy can be considered for anti-CFHAb-associated aHUS. Monitoring of anti-CFHAb titer may help to guide maintenance therapeutic strategies including Rituximab infusion. PMID:27684863

Remission Time after Rituximab Treatment for Autoimmune Bullous Disease: A Proposed Update Definition.

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Iranzo, Pilar; Pigem, Ramon; Giavedoni, Priscila; Alsina-Gibert, Mercè

2015-01-01

A therapeutic endpoint is a very important tool to evaluate response in clinical trials. In 2005, a consensus statement identified two late endpoints of disease activity in pemphigus: complete remission off therapy and complete remission on therapy, both definitions applying to patients without lesions for at least 2 months. The same period of time was considered for partial remission off/on therapy. These definitions were later applied to bullous pemphigoid and are considered in most studies on autoimmune bullous disease. These endpoints were established for different adjuvant agents, but at that moment, rituximab was not considered. Rituximab is known for the long duration of its effect, and in most studies relapses have been reported later than 6 months after treatment. In our opinion, time to remission after rituximab treatment should be redefined. © 2015 S. Karger AG, Basel.

Beneficial effect of tocilizumab in myasthenia gravis refractory to rituximab.

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Jonsson, Dagur Ingi; Pirskanen, Ritva; Piehl, Fredrik

2017-06-01

Muscle fatigue associated with myasthenia gravis is caused by autoantibodies interfering with neuromuscular transmission. Immunomodulating treatment is widely used in moderate to severe myasthenia, although the use of newer biological drugs except rituximab is rare. We describe the effect of tocilizumab, a blocker of interleukin-6 signalling, in two female myasthenia patients with high titres of serum acetylcholine receptor antibodies and insufficient response to rituximab. The first patient had been treated with high dose immunoglobulins regularly for several years and the second patient had been treated both with different oral immune suppressants and immunoglobulins before testing a low dose of rituximab without significant clinical effect. Subsequent treatment with tocilizumab resulted in clinical improvement within a few months. The first patient was switched back to rituximab, which resulted in worsening until tocilizumab was restarted. Tocilizumab can be a therapeutic option in cases not responding to rituximab. Copyright © 2017 Elsevier B.V. All rights reserved.

Neuromyelitis optica spectrum disorders: long-term safety and efficacy of rituximab in Caucasian patients.

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Radaelli, M; Moiola, L; Sangalli, F; Esposito, F; Barcella, V; Ferrè, L; Rodegher, M; Colombo, B; Fazio, R; Martinelli, V; Comi, G

2016-04-01

To assess the long-term benefit-risk profile of repeated courses of rituximab in Caucasian patients affected by neuromyelitis optica (NMO) and related disorders, in everyday clinical practice. This is a prospective observational study performed at San Raffaele Hospital, Milan, Italy. From February 2006, we recruited 21 patients affected by NMO and NMO spectrum of disorders (NMOSD) whom underwent at least one cycle of intravenous (i.v.) rituximab and then were followed for at least 2 years. At a mean follow-up time of 48 months, we observed a significant reduction of the annualized relapse rate (ARR), from 2.0 to 0.16 (p < 0.01); and of the median Expanded Disability Status Scale (EDSS), from 5.5 to 4.0 (p < 0.013). There were 12 patients (57%) who remained disease free during the follow-up period. Five patients (24%) reported mild hematological adverse events. Serious infectious adverse events were reported by another four patients: These were all wheelchair bound at the beginning of their rituximab treatment. A fixed treatment scheme of rituximab, with re-treatment every 6 months, was efficacious for NMO and NMOSD, with a good safety profile; however, to obtain an even better benefit-risk ratio, close monitoring of CD19(+) B cells should be performed before the re-treatment of patients with high-level disability, concomitant leukopenia and hypogammaglobulinemia. © The Author(s), 2015.

Rapid-infusion rituximab in lymphoma treatment: 2-year experience in a single institution.

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Atay, Sevcan; Barista, Ibrahim; Gundogdu, Fatma; Akgedik, Kiymet; Arpaci, Afey

2012-05-01

Rituximab is a chimeric anti-CD20 monoclonal antibody. We aimed to explore the safety and tolerability of rapid infusion rituximab, (over 90 minutes) in patients with non-Hodgkin's lymphoma at Hacettepe University Department of Medical Oncology. Adult patients diagnosed with non-Hodgkin's lymphoma who were to receive rituximab were included in the study. The schedule of administration for cycle 1 was unaltered and delivered according to the product monograph. All subsequent cycles were administered over a total infusion time of 90 minutes (20% of the dose in the first 30 minutes, then the remaining 80% over 60 minutes, total dose delivered in 500 mL). All patients were observed for infusion-related reactions during the rituximab infusion, and vital signs were recorded every 15 minutes. From July 2006 to December 2008, 75 patients with non-Hodgkin's lymphoma were treated with rituximab-based chemotherapy. A total of 372 infusions were administered. The majority of patients were treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone, or rituximab only. The 90-minute rituximab infusion schedule was well tolerated, with no grade 3 or 4 infusion-related adverse events observed. A rapid infusion rituximab over 90 minutes is well tolerated and safe when administered as the second and subsequent infusions in the course of therapy.

Rituximab-Based Treatment, HCV Replication, and Hepatic Flares

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Evangelista Sagnelli

2012-01-01

Full Text Available Rituximab, a chimeric mouse-human monoclonal antibody directed to the CD20 antigen expressed on pre-B lymphocytes and mature lymphocytes, causes a profound B-cell depletion. Due to its peculiar characteristics, this drug has been used to treat oncohaematological diseases, B cell-related autoimmune diseases, rheumatoid arthritis, and, more recently, HCV-associated mixed cryoglobulinaemic vasculitis. Rituximab-based treatment, however, may induce an increased replication of several viruses such as hepatitis B virus, cytomegalovirus, varicella-zoster virus, echovirus, and parvovirus B19. Recent data suggest that rituximab-based chemotherapy induces an increase in HCV expression in hepatic cells, which may become a target for a cell-mediated immune reaction after the withdrawal of treatment and the restoration of the immune control. Only a few small studies have investigated the occurrence of HCV reactivation and an associated hepatic flare in patients with oncohaematological diseases receiving R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone. These studies suggest that the hepatic flares are frequently asymptomatic, but life-threatening liver failure occurs in nearly 10% of cases.

Rituximab-based treatment, HCV replication, and hepatic flares.

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Sagnelli, Evangelista; Pisaturo, Mariantonietta; Sagnelli, Caterina; Coppola, Nicola

2012-01-01

Rituximab, a chimeric mouse-human monoclonal antibody directed to the CD20 antigen expressed on pre-B lymphocytes and mature lymphocytes, causes a profound B-cell depletion. Due to its peculiar characteristics, this drug has been used to treat oncohaematological diseases, B cell-related autoimmune diseases, rheumatoid arthritis, and, more recently, HCV-associated mixed cryoglobulinaemic vasculitis. Rituximab-based treatment, however, may induce an increased replication of several viruses such as hepatitis B virus, cytomegalovirus, varicella-zoster virus, echovirus, and parvovirus B19. Recent data suggest that rituximab-based chemotherapy induces an increase in HCV expression in hepatic cells, which may become a target for a cell-mediated immune reaction after the withdrawal of treatment and the restoration of the immune control. Only a few small studies have investigated the occurrence of HCV reactivation and an associated hepatic flare in patients with oncohaematological diseases receiving R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone). These studies suggest that the hepatic flares are frequently asymptomatic, but life-threatening liver failure occurs in nearly 10% of cases.

Rapid-Infusion Rituximab in Lymphoma Treatment: 2-Year Experience in a Single Institution

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Atay, Sevcan; Barista, Ibrahim; Gundogdu, Fatma; Akgedik, Kiymet; Arpaci, Afey

2012-01-01

Purpose: Rituximab is a chimeric anti-CD20 monoclonal antibody. We aimed to explore the safety and tolerability of rapid infusion rituximab, (over 90 minutes) in patients with non-Hodgkin's lymphoma at Hacettepe University Department of Medical Oncology. Patients and Methods: Adult patients diagnosed with non-Hodgkin's lymphoma who were to receive rituximab were included in the study. The schedule of administration for cycle 1 was unaltered and delivered according to the product monograph. All subsequent cycles were administered over a total infusion time of 90 minutes (20% of the dose in the first 30 minutes, then the remaining 80% over 60 minutes, total dose delivered in 500 mL). All patients were observed for infusion-related reactions during the rituximab infusion, and vital signs were recorded every 15 minutes. Results: From July 2006 to December 2008, 75 patients with non-Hodgkin's lymphoma were treated with rituximab-based chemotherapy. A total of 372 infusions were administered. The majority of patients were treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone, or rituximab only. The 90-minute rituximab infusion schedule was well tolerated, with no grade 3 or 4 infusion-related adverse events observed. Conclusion: A rapid infusion rituximab over 90 minutes is well tolerated and safe when administered as the second and subsequent infusions in the course of therapy. PMID:22942806

Crohn's disease complicated by Epstein-Barr virus-driven haemophagocytic lymphohistiocytosis successfully treated with rituximab.

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Thompson, Grace; Pepperell, Dominic; Lawrence, Ian; McGettigan, Benjamin David

2017-02-22

We report a case of Epstein-Barr virus (EBV)-driven haemophagocytic lymphohistiocytosis (HLH) in a man with Crohn's disease treated with 6-mercaptopurine and adalimumab therapy who was successfully treated with rituximab therapy alone. This is the first published case in an adult patient with EBV-driven HLH in the setting of thiopurine use and inflammatory bowel disease to be successfully treated with rituximab therapy alone. Here, we will discuss putative immunological mechanisms which may contribute to this potentially life-threatening complication. 2017 BMJ Publishing Group Ltd.

Rituximab: a novel treatment for refractory Riedel’s thyroiditis

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Leanne Hunt

2018-02-01

Full Text Available This case report reviews the rare condition of Riedel’s thyroiditis via a patient case. The report highlights the difficulties that one may encounter when managing such a case in regards to patient symptoms, side effects of medications and the relapsing nature of the condition. The case report also highlights novel treatment in the treatment of Riedel’s thyroiditis, rituximab, how this works and the resolution of symptoms that we have achieved with our patient on this treatment.

Rituximab Therapy for Severe Cutaneous Leukocytoclastic Angiitis Refractory to Corticosteroids, Cellcept and Cyclophosphamide

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Kamel El-Reshaid

2013-04-01

Full Text Available We report our clinical experience with rituximab in the treatment of 2 patients with idiopathic cutaneous angiitis who relapsed after treatment with high-dose corticosteroids and cyclophosphamide. A 39-year-old woman and a 51-year-old man presented with ulcerating maculopapular rash in both lower limbs which relapsed 6 months after treatment with a combination of high-dose corticosteroids and cyclophosphamide. After treatment with 2 g of rituximab, the first patient has still been in clinical remission for 32 months while the second has finished 28 months. Interestingly, CD19 which had dropped to 0.5% 8 months later in both patients. Despite that, our patients are still in clinical remission. No significant side effects were noted during infusions and up to the period of follow-up. In conclusion, rituximab is a useful and safe agent in the treatment of idiopathic cutaneous angiitis refractory to conventional therapy. Clinical remission persists years after improvement of B-cell suppression.

Intermediate doses of rituximab used as adjuvant therapy in refractory pemphigus

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Pradnya J Londhe

2014-01-01

Full Text Available Background: Rituximab, a monoclonal anti-CD20 antibody, has been used with encouraging results in pemphigus. We describe herein refractory cases of pemphigus vulgaris (n = 23 and pemphigus foliaceus (n = 1 treated with rituximab in addition to steroids and immunosuppressants. Aims: To assess the response to treatment, the duration of clinical remission, serology of the response and adverse effects of rituximab in pemphigus patients. Methods: We recorded observations of 24 patients with pemphigus having either refractory disease in spite of high dose of steroids and immunosuppressants, corticosteroid-dependent disease, strong contraindications to corticosteroids, or severe disease. The patients were treated with infusions of one injection per week for three consecutive weeks of 375 mg of rituximab per m 2 of body-surface area. One similar infusion was repeated after 3 months of 3 rd dose. We observed the clinical outcome after 6 months of 3 rd dose of rituximab and looked for complete healing of cutaneous and mucosal lesions (complete remission. Observations: After follow-up of 7-24 months, five patients showed only partial improvement while 19 of 24 patients had a complete remission 3 months after rituximab. Of these 19 patients, 12 patients achieved complete remission and are off all systemic therapy, and the rest are continuing with no or low dose of steroids with immunosuppressants. Two patients relapsed after initial improvement; one was given moderate dose of oral steroids and immunosuppressant and the other was given repeat single dose of rituximab to control relapse. Conclusion: Rituximab is able to induce a prolonged clinical remission in pemphigus after a single course of four infusions. The high cost and limited knowledge of long term adverse effects are limitations to the use of this biologic agent.

Relapse of nephrotic syndrome during post-rituximab peripheral blood B-lymphocyte depletion.

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Sato, Mai; Kamei, Koichi; Ogura, Masao; Ishikura, Kenji; Ito, Shuichi

2018-02-01

Rituximab is effective against complicated childhood steroid-dependent nephrotic syndrome (SDNS). Peripheral blood B-lymphocyte (B-cell) depletion is strongly correlated with persistent remission, relapse rarely occurring during B-cell depletion; however, we have encountered several such patients. We retrospectively analyzed the characteristics and clinical course of 82 patients with SDNS treated with rituximab from January 2007 to December 2012 in our institution. Six of 82 patients (7.3%) had relapses during B-cell depletion after receiving rituximab (relapsed group). The remaining 76 patients did not have relapses during B-cell depletion (non-relapsed group). The median time to initial relapse during B-cell depletion was 85 days after receiving rituximab, which is significantly shorter than in the non-relapsed group (410 days, p = 0.0003). The median annual numbers of relapses after receiving rituximab were 2.5 and 0.9 in the relapsed and non-relapsed groups, respectively (p depletion did not differ between the two groups. Relapse during B-cell depletion after receiving rituximab suggests that various pathophysiological mechanisms play a part in childhood nephrotic syndrome.

B-lymphocyte reconstitution after repeated rituximab treatment in a child with steroid-dependent autoimmune hemolytic anemia

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Annelieke A.A. van der Linde

2011-12-01

Full Text Available We report the detailed long-term reconstitution of B-lymphocyte subpopulations, immunoglobulins, and specific antibody production after two courses of rituximab in a young, previously healthy girl with steroid-dependent autoimmune hemolytic anemia. B-lymphocyte subpopulations were surprisingly normal directly after reconstitution. However, there was a slower reconstitution after the second rituximab course, especially of non-switched and switched memory B-lymphocytes, and a temporary decline in IgM below age-matched reference values.

Rituximab chimeric anti-CD20 monoclonal antibody treatment for adult refractory idiopathic thrombocytopenic purpura

DEFF Research Database (Denmark)

Braendstrup, Peter; Bjerrum, Ole W; Nielsen, Ove J

2005-01-01

. Recent studies have shown that rituximab, a chimeric anti-CD20 monoclonal antibody, is useful in the treatment of these patients, with overall response rates of about 50%. Most published reports have included a small number patients including case reports. The present study reports the results...

Neurophysiological and clinical responses to rituximab in patients with anti-MAG polyneuropathy.

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Zara, Gabriella; Zambello, Renato; Ermani, M

2011-12-01

Rituximab treatment has shown clinical improvement in anti-myelin associated glycoprotein (MAG) polyneuropathy. We analyzed scores of clinical scales and the most sensitive electrophysiological parameters before and after immunomodulating treatment with rituximab in a group of patients affected by anti-MAG demyelinating polyneuropathy. Clinical scores, the percentage of CD20 B-lymphocytes, anti-MAG antibody titers and electrophysiological data in 7 patients with anti-MAG polyneuropathy were analyzed. The patients were examined before a cycle with rituximab, 6, 12 and 24 months after the end of the treatment. Two patients were treated with rituximab additional cycles and re-evaluated 48 months after the first treatment. There were no evident correlation between anti-MAG serum antibody titers or clinical scales and electrodiagnostic data. Significant decrease in the proportion of CD20 B-lymphocytes was observed. Significant anti-MAG antibodies titers reduction was detected after re-treatment. At follow-up, pinprik sensation and two point discrimination presented a significant improvement compared with the score before treatment. In our patients, rituximab did not improve any electrophysiological data. No correlation with anti-MAG serum antibodies course was found. With rituximab only pin sensibility improved. Rituximab re-treatment significantly reduces anti-MAG serum antibodies titers but improves only small fibers sensibility. Copyright © 2011 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

Eficiency of different doses of rituximab in rheumatoid arthritis.

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Mena-Vázquez, Natalia; Manrique-Arija, Sara; Ureña-Garnica, Inmaculada; Romero-Barco, Carmen M; Jiménez-Núñez, Francisco G; Coret, Virginia; Irigoyen-Oyarzábal, María Victoria; Fernández-Nebro, Antonio

2016-01-01

Evaluate the effectiveness, cost and safety of rituximab in patients with rheumatoid arthritis (RA) depending on the dose used. Retrospective observational study conducted on 52 patients with RA treated with at least one dose of rituximab for 135.3 patient-years were included. Three treatment groups were obtained: (G1) First course and following two 1g infusions separated by 15 days; (G2) First course 2 infusions of 1g followed by 2 infusions of 500mg; (G3) First course and followed by 2 infusions of 500mg separated by 15 days. Re-treatments were administered on-demand according to the clinical activity. The retention time (Log-Rank), retreats and adverse events rates (incidence rate ratio) and treatment costs per patient-month of rituximab were analysed by groups. Group 2 showed a better cost-effectiveness ratio than group 1, as it was associated with a longer retention of rituximab (mean [95% CI] 65.7 [60.8 to 70.7] months vs 33.5 [22.7 to 44.3]; P<.001) and a lower rate of severe adverse events with only a slight increase in the rate of retreatment (courses/patient-year [95% CI] 1.66 [1.39 to 1.93] vs. 1.01 [0.69 to 1.34]; P=.005), and in the costs (median/patient-month, €484.89 vs. €473.45). Although group 3 was €41.20/patient-month cheaper than group 2, it was associated with a higher rate of re-treatments and shorter retention of rituximab (P<.001). The use of full-dose rituximab at onset, followed by reduced doses in successive courses administered on-demand retreatment may be the most cost-effective option. Copyright © 2015 Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.

Critical appraisal of rituximab in the maintenance treatment of advanced follicular lymphoma

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Aguiar-Bujanda D

2015-10-01

Full Text Available David Aguiar-Bujanda, María Jesús Blanco-Sánchez, María Hernández-Sosa, Saray Galván-Ruíz, Samuel Hernández-Sarmiento Department of Medical Oncology, Hospital Universitario de Gran Canaria Doctor Negrín, Las Palmas de Gran Canaria, Spain Abstract: Rituximab is an IgG1, chimeric monoclonal antibody specifically designed to recognize the CD20 antigen expressed on the surface of normal and malignant B-lymphocytes, from the B-cell precursor to the mature B-cells of the germinal center, and by most neoplasms derived from B-cells. After 2 decades of use, rituximab is firmly positioned in the treatment of follicular lymphoma (FL, both in the front line and in the relapsing disease, improving previous results by including it in classical chemotherapy regimens. However, the pharmacology of rituximab continues to generate controversial issues especially regarding the mechanisms of action in vivo. The contribution of rituximab as a maintenance treatment in FL has been significant progress in the management of this disease without an increase in side effects or a decrease in the quality of life of patients. With the widespread use of rituximab, there are new security alerts and side effects not previously detected in the pivotal trials that clinicians should learn to recognize and manage. In this article, we will review the pharmacokinetics and pharmacodynamics of rituximab, the management issues in the treatment of advanced FL focusing on maintenance rituximab, its long-term efficacy and safety profile, and its effect on the quality of life. Keywords: follicular lymphoma, long-term efficacy, maintenance, rituximab, toxicity

B-cell depletion with rituximab in the treatment of autoimmune diseases. Graves' ophthalmopathy the latest addition to an expanding family

DEFF Research Database (Denmark)

Nielsen, Claus H; El Fassi, Daniel; Hasselbalch, Hans K

2007-01-01

In this review, the authors summarise the clinical results obtained after therapy with rituximab in autoimmune diseases, including Graves' disease and Graves' ophthalmopathy. On the basis of qualitative and quantitative analyses of B- and T-cell subsets, and autoantibody levels obtained in other...... diseases before and after rituximab therapy, the authors interpret the results of the only two clinical investigations of the efficacy of rituximab in the treatment of Graves' disease and Graves' opthalmopathy reported so far. No significant effect on autoantibody levels was observed. Nonetheless, 4 out...... of 10 Graves' disease patients remained in remission 400 days after rituximab treatment versus none in the control group, and remarkable improvements in the eye symptoms of patients with Graves' ophthalmopathy were observed. This supports a role for B cells in the pathogenesis of Graves' ophthalmopathy...

Posterior reversible encephalopathy syndrome masquerading as progressive multifocal leukoencephalopathy in rituximab treated neuromyelitis optica.

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Berger, Joseph R; Neltner, Janna; Smith, Charles; Cambi, Franca

2014-11-01

Both progressive multifocal leukoencephalopathy (PML) and posterior reversible encephalopathy syndrome (PRES) have been reported as complications of rituximab therapy. These disorders may appear indistinguishable on magnetic resonance imaging (MRI). We report on a 42 year old woman with neuromyelitis optica (NMO) of 10 years duration who developed extensive white matter disease affecting chiefly both parietal lobes 6 months after her first and only dose of rituximab. The MRI findings suggested the diagnosis of PML, but her history was more consistent with PRES. Ultimately, a brain biopsy was performed which was consistent with the diagnosis of PRES. PRES and PML may have overlapping symptomatology and be indistinguishable on MRI. An approach to distinguishing between these two disorders is addressed. Copyright © 2014. Published by Elsevier B.V.

Benefit from B-lymphocyte depletion using the anti-CD20 antibody rituximab in chronic fatigue syndrome. A double-blind and placebo-controlled study.

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Øystein Fluge

Full Text Available Chronic fatigue syndrome (CFS is a disease of unknown aetiology. Major CFS symptom relief during cancer chemotherapy in a patient with synchronous CFS and lymphoma spurred a pilot study of B-lymphocyte depletion using the anti-CD20 antibody Rituximab, which demonstrated significant clinical response in three CFS patients.In this double-blind, placebo-controlled phase II study (NCT00848692, 30 CFS patients were randomised to either Rituximab 500 mg/m(2 or saline, given twice two weeks apart, with follow-up for 12 months. Xenotropic murine leukemia virus-related virus (XMRV was not detected in any of the patients. The responses generally affected all CFS symptoms. Major or moderate overall response, defined as lasting improvements in self-reported Fatigue score during follow-up, was seen in 10 out of 15 patients (67% in the Rituximab group and in two out of 15 patients (13% in the Placebo group (p = 0.003. Mean response duration within the follow-up period for the 10 responders to Rituximab was 25 weeks (range 8-44. Four Rituximab patients had clinical response durations past the study period. General linear models for repeated measures of Fatigue scores during follow-up showed a significant interaction between time and intervention group (p = 0.018 for self-reported, and p = 0.024 for physician-assessed, with differences between the Rituximab and Placebo groups between 6-10 months after intervention. The primary end-point, defined as effect on self-reported Fatigue score 3 months after intervention, was negative. There were no serious adverse events. Two patients in the Rituximab group with pre-existing psoriasis experienced moderate psoriasis worsening.The delayed responses starting from 2-7 months after Rituximab treatment, in spite of rapid B-cell depletion, suggests that CFS is an autoimmune disease and may be consistent with the gradual elimination of autoantibodies preceding clinical responses. The present findings will impact

Long-term treatment with rituximab in severe juvenile idiopathic arthritis-associated uveitis.

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Miserocchi, Elisabetta; Modorati, Giulio; Berchicci, Luigi; Pontikaki, Irene; Meroni, Pierluigi; Gerloni, Valeria

2016-06-01

To evaluate retrospectively the long-term efficacy of rituximab in patients with severe juvenile idiopathic arthritis (JIA)-associated uveitis. Eight patients (15 eyes) with severe and longstanding JIA uveitis, who had an inadequate response in controlling uveitis to one or more biologic agents including tumour necrosis factor blockers and abatacept, received rituximab therapy. Rituximab was given at a dose of 1000 mg per infusion on days 1 and 15 and then every 6 months. Clinical responses to treatment, including decrease in uveitis activity, visual acuity changes, reduction of concomitant local and systemic corticosteroid and/or immunosuppressants, and occurrence of adverse events, were assessed. Eight patients with a mean±SD age of 22.8±5.5 years were treated. The mean ocular disease duration was 17.7 years; the mean±SD follow-up time on rituximab was 44.75±4.9 months; and the mean number of rituximab infusions received was 8.75 (range 6-12). All patients achieved complete control of uveitis, but in two patients rituximab was discontinued due to inefficacy in treating arthritis. The decrease in uveitis activity was evident 4-5 months after the first infusion. Systemic corticosteroids and immunosuppressants used in association with rituximab were discontinued in five patients at the end of follow-up. None of the patients experienced visual worsening during the follow-up. No drug-related complications were encountered. Rituximab may be a promising effective treatment option for refractory uveitis associated with JIA leading to long-term quiescence of uveitis, particularly for patients who have not previously responded to other biologic therapies. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Rituximab maintenance for 2 years in patients with high tumour burden follicular lymphoma responding to rituximab plus chemotherapy (PRIMA): a phase 3, randomised controlled trial

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Salles, Gilles; Seymour, John Francis; Offner, Fritz

2011-01-01

Patients with follicular lymphoma can have long survival times, but disease progression typically occurs 3-5 years after initial treatment. We assessed the potential benefit of 2 years of rituximab maintenance after first-line treatment in patients with follicular lymphoma receiving a rituximab...... plus chemotherapy regimen....

Efficacy and safety of rituximab in neuromyelitis optica: Review of evidence

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Masoud Etemadifar

2017-01-01

Full Text Available Neuromyelitis optica (NMO is an autoimmune inflammatory disease of the central nervous system with preferential involvement in the optic nerve and spinal cord with a widespread spectrum of clinical features; multiple therapeutic agents have been used with different results. Recent evidence points to B-cell-mediated humoral immunity in the pathogenesis of NMO. Rituximab targets the CD20 antigen on B-cells. Treatment leads to profound B-cell depletion, principally over an antibody-dependent cell cytotoxicity mechanism. The aim of our study was to review clinical trials to elucidate the impact of rituximab on the relapse rate, Expanded Disability Status Scale (EDSS, and progression of disability in NMO. We performed a comprehensive review of all studies that evaluated clinical and paraclinical effects of rituximab on NMO. MEDLINE-PubMed, Web of Sciences, EMBASE, and Cochrane databases up to June 2016 included in our searches. In addition, reference lists from articles identified by search as well as a key review article to identify additional articles included in the study. Rituximab targets the CD20 antigen on B-cells and decreases attack frequency and severity in patients with NMO; however, it does not remove attacks, even when modifying treatment to achieve B-cell depletion. Most of the investigations revealed that EDSS significantly in all patients with rituximab treatment will be decreased after treatment with rituximab. No new or enlarged lesions or pathological gadolinium enhancement was observed in serial brain and spinal cord magnetic resonance imaging, except for those observed concomitantly with clinical relapses and the median length of spinal cord lesions was significantly reduced after therapy. Rituximab targets the CD20 antigen and decreases attack frequency and severity in patients with NMO.

Rituximab and new regimens for indolent lymphoma: a brief update from 2012 ASCO Annual Meeting

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Zhao Jiangning

2012-08-01

Full Text Available Abstract Indolent lymphoma (IL, the second most common lymphoma, remains incurable with chemotherapy alone. While R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone remains the standard frontline regimen for diffuse Large B –cell lymphoma, the optimal chemotherapy regimen for frontline therapy of advanced IL remains uncertain. FCR (fludarabine, cyclophosphamide, rituximab has been shown to be better than fludarabine alone and fludarabine plus cyclophosphamide for IL. In FOLL05 trial, R-CHOP was compared with R-CVP (cyclophosphamide, vincristine, prednisone and R-FM (fludarabine, mitoxantrone. The study showed that R-CHOP appears to have the best risk-benefit ratio for IL. The StiL NHL1 trial showed that BR (bendamustine, rituximab has longer progression free survival and is better tolerated than R-CHOP. Long-term complications with secondary malignancies between the two regimens appear to be comparable. In this review, new combination regimens reported at 2012 ASCO annual meeting were evaluated for frontline and salvage therapy of indolent lymphoma.

Effectiveness of disease-modifying antirheumatic drug co-therapy with methotrexate and leflunomide in rituximab-treated rheumatoid arthritis patients

DEFF Research Database (Denmark)

Chatzidionysiou, Katerina; Lie, Elisabeth; Nasonov, Evgeny

2012-01-01

is an effective and safe alternative to methotrexate as concomitant treatment with rituximab. Slightly better results were obtained by the combination of rituximab and leflunomide than rituximab and methotrexate, raising the possibility of a synergistic effect of leflunomide and rituximab.......OBJECTIVES: To compare the effectiveness and safety of rituximab alone or in combination with either methotrexate or leflunomide.METHODS: 10 European registries submitted anonymised datasets with baseline, 3, 6, 9 and 12-month clinical data from patients who started rituximab.RESULTS: 1195 patients...

Efficacy and safety of different doses and retreatment of rituximab: a randomised, placebo-controlled trial in patients who are biological naive with active rheumatoid arthritis and an inadequate response to methotrexate (Study Evaluating Rituximab's Efficacy in MTX iNadequate rEsponders (SERENE)).

Science.gov (United States)

Emery, P; Deodhar, A; Rigby, W F; Isaacs, J D; Combe, B; Racewicz, A J; Latinis, K; Abud-Mendoza, C; Szczepanski, L J; Roschmann, R A; Chen, A; Armstrong, G K; Douglass, W; Tyrrell, H

2010-09-01

This phase III study evaluated the efficacy and safety of rituximab plus methotrexate (MTX) in patients with active rheumatoid arthritis (RA) who had an inadequate response to MTX and who were naïve to prior biological treatment. Patients with active disease on stable MTX (10-25 mg/week) were randomised to rituximab 2 x 500 mg (n=168), rituximab 2 x 1000 mg (n=172), or placebo (n=172). From week 24, patients not in remission (Disease Activity Score (28 joints) > or =2.6) received a second course of rituximab; patients initially assigned to placebo switched to rituximab 2 x 500 mg. The primary end point was American College of Rheumatology 20 (ACR20) response at week 24. All patients were followed until week 48. At week 24, both doses of rituximab showed statistically superior efficacy (p<0.0001) to placebo (ACR20: 54%, 51% and 23%; rituximab (2 x 500 mg) + MTX, rituximab (2 x 1000 mg) + MTX and placebo + MTX, respectively). Secondary end points were also significantly improved for both rituximab groups compared with placebo. Further improvements in both rituximab arms were observed from week 24 to week 48. Rituximab + MTX was well tolerated, demonstrating comparable safety to placebo + MTX through to week 24, and between rituximab doses through to week 48. Rituximab (at 2 x 500 mg and 2 x 1000 mg) plus MTX significantly improved clinical outcomes at week 24, which were further improved by week 48. No significant differences in either clinical or safety outcomes were apparent between the rituximab doses.

Progression of structural damage is not related to rituximab serum levels in rheumatoid arthritis patients

NARCIS (Netherlands)

Boumans, Maria; Teng, Onno; Thurlings, Rogier; Bijlsma, Johannes; Gerlag, Danielle; Huizinga, Tom; Vos, Koen; Stapel, Steven; Wolbink, Gertjan; Tekstra, Janneke; van Laar, Jaap; Tak, Paul P.

2013-01-01

The most cost-effective dosing regimen for rituximab treatment in RA is currently unknown. The objective of this study is to determine whether low rituximab serum levels are associated with progression of structural damage in RA patients. Sixty-two RA patients were treated with rituximab in three

Trombocitopenia de difícil manejo en niño preescolar con LES: Reporte de un caso

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Mario Nicolás Albani Pérez

2010-08-01

Full Text Available El lupus eritematoso sistémico (LES es una enfermedad autoinmune del tejido conectivo, infrecuente en el sexo masculino y durante la infancia. La trombocitopenia se presenta en 15% de los casos de LES, y como forma de inicio es poco común. Se reporta el caso de preescolar masculino de 3 años de edad con inicio de enfermedad a los 18 meses de edad que presentó diarrea, rash cutáneo, equimosis y trombocitopenia; ameritando transfusión de concentrado plaquetario obteniendo mejoría parcial y en control con hematólogo. A los  2 años de edad reaparece equimosis y se diagnostica Púrpura Trombocitopénica Idiopática, tratado con inmunoglobulinas y esteroides sin respuesta satisfactoria. Es referido a Inmunología donde solicitan estudios y los resultados son compatibles con LES, por lo cual recibió prednisona sin respuesta satisfactoria. En Febrero de 2009, presenta epistaxis requiriendo hospitalización y tratamiento con inmunoglobulinas. En Mayo de 2009, presenta otorragia derecha ameritando nuevamente hospitalización y tratamiento con inmunoglobulinas. Se emplea Danazol con buena respuesta. En caso que en el futuro no ofrezca mejoría, se plantea el uso alternativo de ciclosporinas o anticuerpos monoclonales Anti-CD20 (Rituximab dejando como último recurso la esplenectomía. Se presenta el caso clínico considerando la importancia con respecto a la edad de presentación y el manejo no convencional que se debió adoptar para tratar al paciente.

Trombocitopenia de difícil manejo en niño preescolar con LES: Reporte de un caso

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Mario Nicolás Albani Pérez

2009-01-01

Full Text Available El lupus eritematoso sistémico (LES es una enfermedad autoinmune del tejido conectivo, infrecuente en el sexo masculino y durante la infancia. La trombocitopenia se presenta en 15% de los casos de LES, y como forma de inicio es poco común. Se reporta el caso de preescolar masculino de 3 años de edad con inicio de enfermedad a los 18 meses de edad que presentó diarrea, rash cutáneo, equimosis y trombocitopenia, ameritando transfusión de concentrado plaquetario obteniendo mejoría parcial y en control con hematólogo. A los 2 años de edad reaparece equimosis y se diagnostica Púrpura Trombocitopénica Idiopática, tratado con inmunoglobulinas y esteroides sin respuesta satisfactoria. Es referido a Inmunología donde solicitan estudios y los resultados son compatibles con LES, por lo cual recibió prednisona sin respuesta satisfactoria. En Febrero de 2009, presenta epistaxis requiriendo hospitalización y tratamiento con inmunoglobulinas. En Mayo de 2009, presenta otorragia derecha ameritando nuevamente hospitalización y tratamiento con inmunoglobulinas. Se emplea Danazol con buena respuesta. En caso que en el futuro no ofrezca mejoría, se plantea el uso alternativo de ciclosporinas o anticuerpos monoclonales Anti- CD20 (Rituximab dejando como último recurso la esplenectomía. Se presenta el caso clínico considerando la importancia con respecto a la edad de presentación y el manejo no convencional que se debió adoptar para tratar al paciente.

Study On The Preparation Of 90Y-DTPA-Rituximab For Non-Hodgkin Lymphoma Treatment

International Nuclear Information System (INIS)

Nguyen Thi Thu; Duong Van Dong; Bui Van Cuong; Vo Thi Cam Hoa; Chu Van Khoa; Phan Quoc Thong

2011-01-01

Yttrium is one of the most useful radionuclides for radioimmunotherapeutic applications, especially labelling with monoclonal antibodies. Rituximab was bound to the DTPA chelating agent using Hnatowich methods. Cyclic anhydride DTPA (cDTPAa, 0.1 mg/ml) was dissolved in chloroform and was degassed under a stream of nitrogen for 30 minutes. Rituximab solution in 0.05 M bicarbonate buffer was immediately added and mixed for one minute at room temperature. The antibody Rituximab at different concentration (5 mg/ml and 10 mg/ml) was coupled with the cDTPAa, at molar ratios (cDTPAa : Rituximab) of 1:1, 3:1, 5:1, 10:1 and 20:1. The conjugation of DTPA-Rituximab mixture was labelled with Y-90, then using Sephadex G25 in order to determine coupling efficiency. Coupling efficiency at a 3:1 mole ratio was 70%. After purification, the conjugation DTPA-Rituximab was labeled with Y-90 in 0.5 M acetate buffer, pH 5, at room temperature. The labeling yield was about 99%. The radiochemical purity of 90 Y-DTPA-Rituximab was more than 98 % which determined by ITLC in 0.1 M acetate at pH 6 as mobile phase. The radiopharmaceuticals have been test for sterility, apyrogenicity and biodistribution. This is a potential radiopharmaceutical for clinical application in therapeutic Non Hodgkin Lymphoma treatments. (author)

Rituximab-induced interstitial lung disease

DEFF Research Database (Denmark)

Naqibullah, Matiuallah; Shaker, Saher B; Bach, Karen S

2015-01-01

Rituximab (RTX), a mouse/human chimeric anti-CD20 IgG1 monoclonal antibody has been effectively used as a single agent or in combination with chemotherapy regimen to treat lymphoma since 1997. In addition, it has been used to treat idiopathic thrombocytopenic purpura, systemic lupus erythematous...

Efficacy and Safety of Rituximab in the Treatment of Vasculitic Leg Ulcers Associated with Hepatitis C Virus Infection

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Fabio Bonilla-Abadía

2012-01-01

Full Text Available Vasculitic leg ulcers are a cutaneous manifestation of hepatitis C virus (HCV infection often associated with cryoglobulinemia. Their treatment is difficult and is based on steroids and immunosuppressive drugs with an erratic response and a high probability of adverse reaction. We report three patients with vasculitic leg ulcers associated with hepatitis C virus infection who were treated successfully with rituximab. The pain control and healing were achieved quickly. No adverse effects with rituximab in these patients were presented.

Socioeconomic inequality in the use of rituximab therapy among non-Hodgkin lymphoma patients in Chinese public hospitals.

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Yu-Wen, Huang; Mei-Bian, Zhang; Xiang, Xu; Xiao-Hua, Xu; Quan, Zhou; Le, Jian

2014-03-01

Rituximab is a patient-paid effective monoclonal-antibody drug for non-Hodgkin lymphoma (NHL). Little is known in China, a country with unequal distribution of wealth and medical insurance systems, about the impact of socioeconomic status (SES) on selecting rituximab therapy in NHL patients. A total of 328 NHL inpatients in 2 public hospitals in Hangzhou were recruited and divided into 2 equal groups: with rituximab therapy and with no rituximab therapy group. Selection and frequency of rituximab therapy increased with duration of education and in urban citizens (P inequality in provision of rituximab therapy among Chinese NHL patients, and this was associated with differences in SES status. Effective measures are suggested to ameliorate the inequality issue.

[Rituximab: a new therapeutic alternative in Grave's disease].

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Tello-Winniczuk, Nina; Díaz-Jouanen, Efraín

2011-01-01

Graves' disease is the most frequent cause of hyperthyroidism, affecting mainly young aged women, with an etiology of autoimmune basis. One of its manifestations, Graves' ophthalmopathy whose pathophysiology is unknown, represents one of the greatest therapeutic challenges in these patients, because they require aggressive treatment with steroids and multiple subsequent reconstructive surgeries in certain cases. It also represents a high burden to the health system. Drugs targeting B cells have been very effective for many autoimmune diseases. Rituximab is a murine humanized monoclonal antibody against CD20 + cells currently being studied in various autoimmune diseases including Graves' disease. The objective of this paper is to expose possible mechanisms by which rituximab could act in both hyperthyroidism and ophthalmopathy of Graves' disease, as well as the experience with its use acquired so far. The employment of rituximab in recently diagnosed patients or with mild ophthalmopathy is questionable with the evidence available today however, we think that it may have a role in refractory cases or those who have a contraindication for steroid use.

Muscle myeloid type I interferon gene expression may predict therapeutic responses to rituximab in myositis patients.

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Nagaraju, Kanneboyina; Ghimbovschi, Svetlana; Rayavarapu, Sree; Phadke, Aditi; Rider, Lisa G; Hoffman, Eric P; Miller, Frederick W

2016-09-01

To identify muscle gene expression patterns that predict rituximab responses and assess the effects of rituximab on muscle gene expression in PM and DM. In an attempt to understand the molecular mechanism of response and non-response to rituximab therapy, we performed Affymetrix gene expression array analyses on muscle biopsy specimens taken before and after rituximab therapy from eight PM and two DM patients in the Rituximab in Myositis study. We also analysed selected muscle-infiltrating cell phenotypes in these biopsies by immunohistochemical staining. Partek and Ingenuity pathway analyses assessed the gene pathways and networks. Myeloid type I IFN signature genes were expressed at higher levels at baseline in the skeletal muscle of rituximab responders than in non-responders, whereas classic non-myeloid IFN signature genes were expressed at higher levels in non-responders at baseline. Also, rituximab responders have a greater reduction of the myeloid and non-myeloid type I IFN signatures than non-responders. The decrease in the type I IFN signature following administration of rituximab may be associated with the decreases in muscle-infiltrating CD19(+) B cells and CD68(+) macrophages in responders. Our findings suggest that high levels of myeloid type I IFN gene expression in skeletal muscle predict responses to rituximab in PM/DM and that rituximab responders also have a greater decrease in the expression of these genes. These data add further evidence to recent studies defining the type I IFN signature as both a predictor of therapeutic responses and a biomarker of myositis disease activity. Published by Oxford University Press on behalf British Society for Rheumatology 2016. This work is written by US Government employees and is in the public domain in the US.

Efficacy and safety of different doses and retreatment of rituximab: a randomised, placebo-controlled trial in patients who are biological naïve with active rheumatoid arthritis and an inadequate response to methotrexate (Study Evaluating Rituximab's Efficacy in MTX iNadequate rEsponders (SERENE))

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Emery, P; Deodhar, A; Rigby, W F; Isaacs, J D; Combe, B; Racewicz, A J; Latinis, K; Abud-Mendoza, C; Szczepański, L J; Roschmann, R A; Chen, A; Armstrong, G K; Douglass, W; Tyrrell, H

2010-01-01

Objectives This phase III study evaluated the efficacy and safety of rituximab plus methotrexate (MTX) in patients with active rheumatoid arthritis (RA) who had an inadequate response to MTX and who were naïve to prior biological treatment. Methods Patients with active disease on stable MTX (10–25 mg/week) were randomised to rituximab 2×500 mg (n=168), rituximab 2×1000 mg (n=172), or placebo (n=172). From week 24, patients not in remission (Disease Activity Score (28 joints) ≥2.6) received a second course of rituximab; patients initially assigned to placebo switched to rituximab 2×500 mg. The primary end point was American College of Rheumatology 20 (ACR20) response at week 24. All patients were followed until week 48. Results At week 24, both doses of rituximab showed statistically superior efficacy (p<0.0001) to placebo (ACR20: 54%, 51% and 23%; rituximab (2×500 mg) + MTX, rituximab (2×1000 mg) + MTX and placebo + MTX, respectively). Secondary end points were also significantly improved for both rituximab groups compared with placebo. Further improvements in both rituximab arms were observed from week 24 to week 48. Rituximab + MTX was well tolerated, demonstrating comparable safety to placebo + MTX through to week 24, and between rituximab doses through to week 48. Conclusions Rituximab (at 2×500 mg and 2×1000 mg) plus MTX significantly improved clinical outcomes at week 24, which were further improved by week 48. No significant differences in either clinical or safety outcomes were apparent between the rituximab doses. PMID:20488885

Ibrutinib combined with bendamustine and rituximab compared with placebo, bendamustine, and rituximab for previously treated chronic lymphocytic leukaemia or small lymphocytic lymphoma (HELIOS): a randomised, double-blind, phase 3 study.

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Chanan-Khan, Asher; Cramer, Paula; Demirkan, Fatih; Fraser, Graeme; Silva, Rodrigo Santucci; Grosicki, Sebastian; Pristupa, Aleksander; Janssens, Ann; Mayer, Jiri; Bartlett, Nancy L; Dilhuydy, Marie-Sarah; Pylypenko, Halyna; Loscertales, Javier; Avigdor, Abraham; Rule, Simon; Villa, Diego; Samoilova, Olga; Panagiotidis, Panagiots; Goy, Andre; Mato, Anthony; Pavlovsky, Miguel A; Karlsson, Claes; Mahler, Michelle; Salman, Mariya; Sun, Steven; Phelps, Charles; Balasubramanian, Sriram; Howes, Angela; Hallek, Michael

2016-02-01

-free survival. Crossover to ibrutinib was permitted for patients in the placebo group with IRC-confirmed disease progression. Analysis was by intention-to-treat and is continuing for further long-term follow-up. The trial is registered with ClinicalTrials.gov, number NCT01611090. Between Sept 19, 2012, and Jan 21, 2014, 578 eligible patients were randomly assigned to ibrutinib or placebo in combination with bendamustine plus rituximab (289 in each group). The primary endpoint was met at the preplanned interim analysis (March 10, 2015). At a median follow-up of 17 months (IQR 13·7-20·7), progression-free survival was significantly improved in the ibrutinib group compared with the placebo group (not reached in the ibrutinib group (95% CI not evaluable) vs 13·3 months (11·3-13·9) in the placebo group (hazard ratio [HR] 0·203, 95% CI 0·150-0·276; pibrutinib group and 24% (18-31) in the placebo group (HR 0·203, 95% CI 0·150-0·276; pibrutinib group and 212 (74%) of 287 patients in the placebo group reported grade 3-4 events; the most common grade 3-4 adverse events in both groups were neutropenia (154 [54%] in the ibrutinib group vs 145 [51%] in the placebo group) and thrombocytopenia (43 [15%] in each group). A safety profile similar to that previously reported with ibrutinib and bendamustine plus rituximab individually was noted. In patients eligible for bendamustine plus rituximab, the addition of ibrutinib to this regimen results in significant improvements in outcome with no new safety signals identified from the combination and a manageable safety profile. Janssen Research & Development. Copyright © 2016 Elsevier Ltd. All rights reserved.

Preclinical activity of the type II CD20 antibody GA101 (obinutuzumab) compared with rituximab and ofatumumab in vitro and in xenograft models.

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Herter, Sylvia; Herting, Frank; Mundigl, Olaf; Waldhauer, Inja; Weinzierl, Tina; Fauti, Tanja; Muth, Gunter; Ziegler-Landesberger, Doris; Van Puijenbroek, Erwin; Lang, Sabine; Duong, Minh Ngoc; Reslan, Lina; Gerdes, Christian A; Friess, Thomas; Baer, Ute; Burtscher, Helmut; Weidner, Michael; Dumontet, Charles; Umana, Pablo; Niederfellner, Gerhard; Bacac, Marina; Klein, Christian

2013-10-01

We report the first preclinical in vitro and in vivo comparison of GA101 (obinutuzumab), a novel glycoengineered type II CD20 monoclonal antibody, with rituximab and ofatumumab, the two currently approved type I CD20 antibodies. The three antibodies were compared in assays measuring direct cell death (AnnexinV/PI staining and time-lapse microscopy), complement-dependent cytotoxicity (CDC), antibody-dependent cell-mediated cytotoxicity (ADCC), antibody-dependent cell-mediated phagocytosis (ADCP), and internalization. The models used for the comparison of their activity in vivo were SU-DHL4 and RL xenografts. GA101 was found to be superior to rituximab and ofatumumab in the induction of direct cell death (independent of mechanical manipulation required for cell aggregate disruption formed by antibody treatment), whereas it was 10 to 1,000 times less potent in mediating CDC. GA101 showed superior activity to rituximab and ofatumumab in ADCC and whole-blood B-cell depletion assays, and was comparable with these two in ADCP. GA101 also showed slower internalization rate upon binding to CD20 than rituximab and ofatumumab. In vivo, GA101 induced a strong antitumor effect, including complete tumor remission in the SU-DHL4 model and overall superior efficacy compared with both rituximab and ofatumumab. When rituximab-pretreated animals were used, second-line treatment with GA101 was still able to control tumor progression, whereas tumors escaped rituximab treatment. Taken together, the preclinical data show that the glyoengineered type II CD20 antibody GA101 is differentiated from the two approved type I CD20 antibodies rituximab and ofatumumab by its overall preclinical activity, further supporting its clinical investigation. ©2013 AACR.

Retrospective analysis of rituximab therapy and splenectomy in childhood chronic and refractory immune thrombocytopenic purpura.

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Ay, Yilmaz; Karapinar, Tuba H; Oymak, Yesim; Toret, Ersin; Demirag, Bengu; Ince, Dilek; Ozcan, Esin; Moueminoglou, Nergial; Koker, Sultan A; Vergin, Canan

2016-06-01

Immune thrombocytopenic purpura (ITP) results from accelerated platelet destruction mediated by autoantibodies to platelet glycoproteins. Some patients with chronic ITP are refractory to all therapies [steroids, intravenous immunoglobulin (IVIG), anti-D and immunosuppresive drugs] and have chronic low platelet counts and episodic bleeding. We retrospectively evaluated the efficacy and safety of rituximab treatment and splenectomy in paediatric patients diagnosed with chronic and refractory ITP who were unresponsive to steroids, IVIG, cyclosporine and mycophenolate mofetil. Records of patients with chronic and refractory ITP in 459 patients with primary ITP who were followed up in our hospital from January 2005 to December 2014 were reviewed. Fifteen of patients received rituximab and/or applied splenectomy. Fifteen chronic ITP patients (10 boys, five girls) with a mean age of 10 years were enrolled in the study. Two of these patients were suffering from Evans syndrome. The median time since diagnosis of ITP was 10 years. The median follow-up duration after starting Rituximab and splenectomy were 13 and 9.5 months, respectively.None of the seven patients who were treated with rituximab achieved a response. A splenectomy was performed in six of the seven patients who had been treated with rituximab. Complete and partial responses were achieved in 67 and 33% of the patients, respectively. We evaluated the clinical characteristics and responses of chronic ITP patients who did not receive rituximab therapy and underwent a splenectomy. The success rate was 100% in the eight patients with chronic and refractory ITP. Rituximab therapy might not be beneficial for some children with severe chronic ITP who are refractory to standard agents. A splenectomy might be useful and preferable to rituximab.

99mTc-rituximab radiolabelled by photo-activation: a new non-Hodgkin's lymphoma imaging agent

International Nuclear Information System (INIS)

Gmeiner Stopar, T.; Fettich, J.; Hojker, S.; Mlinaric-Rascan, I.; Mather, S.J.

2006-01-01

Rituximab was the first chimeric monoclonal antibody to be approved for treatment of indolent B-cell non-Hodgkin's lymphoma (NHL). It is directed against the CD20 antigen, which is expressed by 95% of B-cell NHLs. The aim of this study was to explore the possibility of radiolabelling rituximab with 99m Tc for use as an imaging agent in NHL for early detection, staging, remission assessment, monitoring for metastatic spread and tumour recurrence, and assessment of CD20 expression prior to (radio)immunotherapy. Rituximab was purified from Mabthera solution (Roche), photo-activated at 302 nm by UV irradiation and radiolabelled with 99m Tc. The effectiveness of the labelling method was evaluated by determination of the number of free thiol groups per photoreduced antibody, radiochemical purity and in vitro stability of 99m Tc-rituximab. On average, 4.4 free thiol groups per photoreduced antibody were determined. Radiolabelling yields greater than 95% were routinely observed after storage of the photo-activated antibody at -80 C for 195 days. The direct binding assay showed preserved ability of 99m Tc-rituximab to bind to CD20, with an average immunoreactive fraction of 93.3%. The internalisation rate was proven to be low, with only 5.3% of bound 99m Tc-rituximab being internalised over 4 h at 37 C. Our results demonstrate that 99m Tc-rituximab of high radiochemical purity and with preserved binding affinity for the antigen can be prepared by photoreduction and that the method shows good reproducibility. 99m Tc-rituximab will be further explored as an imaging agent applicable in NHL for the purposes mentioned above. (orig.)

RITUXIMAB: NEW POTENTIALITIES OF THERAPY FOR RHEUMATOID ARTHRITIS

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D E Karateev

2008-01-01

Full Text Available Some patients with rheumatoid arthritis (RA are unresponsive or intolerant to both synthetic first-line anti-inflammatory drugs (FLAID and tumor necrosis factor (TNF а inhibitors already included into all the treatment standards . Along with the conventional methods for overcoming drug resistance - switching to another FLAID or another TNF а blocker, the use of biologicals with another mechanism of action rather than suppression of TNF а gives a good account of itself. Prominent among these agents is the anti-B-cell drug rituximab. The new possibilities of the therapy, which open up the use of rituximab in patients with RA, are discussed.

Rituximab treatment in primary angiitis of the central nervous system.

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Patel, Shreeya; Ross, Laura; Oon, Shereen; Nikpour, Mandana

2018-06-01

Primary angiitis of the central nervous system (PACNS) is a rare autoimmune vasculitis affecting the brain and spinal cord. Treatment with biological agents has revolutionised the treatment of many rheumatic conditions but there is scant literature regarding the use of biological agents in PACNS. We present three cases of PACNS treated with rituximab, including two cases of relapsed disease, and a literature review suggesting a role for rituximab in this condition. © 2018 Royal Australasian College of Physicians.

Severe infection in patients with rheumatoid arthritis taking anakinra, rituximab, or abatacept: a systematic review of observational studies.

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Cabral, Vanderlea Poeys; Andrade, Carlos Augusto Ferreira de; Passos, Sonia Regina Lambert; Martins, Maria de Fátima Moreira; Hökerberg, Yara Hahr Marques

A question is raised about an increased risk of severe infection from the use of biological drugs in patients with rheumatoid arthritis. This systematic review of observational studies aimed at assessing the risk of severe infection associated with the use of anakinra, rituximab, and abatacept in patients with rheumatoid arthritis. The following databases were searched: PubMed, Science Direct, Scopus, Web of Knowledge, Scirus, Cochrane, Exerpta Medica Database, Scielo, and Lilacs up to July 2010. Severe infections were defined as those life-threatening ones in need of the use of parenteral antibiotics or of hospitalization. Longitudinal observational studies were selected without language restriction, involving adult patients diagnosed with rheumatoid arthritis and who used anakinra, rituximab, or abatacept. In four studies related to anakinra, 129 (5.1%) severe infections were related in 2896 patients, of which three died. With respect to rituximab, two studies reported 72 (5.9%) severe infections in 1224 patients, of which two died. Abatacept was evaluated in only one study in which 25 (2.4%) severe infections were reported in 1046 patients. The main site of infection for these three drugs was the respiratory tract. One possible explanation for the high frequency of severe infections associated with anakinra may be the longer follow-up time in the selected studies. The high frequency of severe infections associated with rituximab could be credited to the less strict inclusion criteria for the patients studied. Therefore, infection monitoring should be cautious in patients with rheumatoid arthritis in use of these three drugs. Copyright © 2016. Published by Elsevier Editora Ltda.

Fulminante, rituximab-resistente, mucocutane pemphigus vulgaris

NARCIS (Netherlands)

Gostyński, A.; Ammatuna, E.; Huls, G.; Wouthuyzen-Bakker, M.; Jonkman, M. F.; Horváth, B.

2017-01-01

Pemphigus vulgaris is an autoimmune disease mediated by auto-antibodies against desmoglein 1 and 3. First line treatment for pemphigus consists of systemic corticosteroids and anti-CD20 therapy (rituximab) to eliminate B-cells. Since 2005, more than 100 patients with pemphigus have been treated with

Intralesional rituximab in primary conjunctival follicular lymphoma relapsed.

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Rodríguez Villa, S; Ruiz Rodríguez, M J; Vargas Pabón, M

2017-07-01

A 49-year-old woman experienced a local relapse of a primary follicular lymphoma (FL) of the conjunctiva. She received 4 weekly intra-lesional injections followed by 6 monthly injections of rituximab (6mg/ml). A clinical response was achieved after first injection. No adverse ocular event or signs of lymphoma relapse were seen after 10 months of follow-up. Intralesional administration of rituximab for treating primary FL of the conjunctiva was an effective and safe therapeutic option; therefore it could be an alternative to other conventional treatments, such as radiotherapy or chemotherapy. Copyright © 2016 Sociedad Española de Oftalmología. Publicado por Elsevier España, S.L.U. All rights reserved.

Time-Dependent Structural Alteration of Rituximab Analyzed by LC/TOF-MS after a Systemic Administration to Rats.

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Yuki Otani

Full Text Available Therapeutic monoclonal antibodies (mAbs have heterogeneities in their structures. Multiple studies have reported that the variety of post-translational modifications could affect the pharmacokinetic profiles or pharmacological potencies of therapeutic mAbs. Taking into the account that the structural modification of mAbs would affect the efficacy, it is worth investigating the structural alteration of therapeutic mAbs in the blood and the relationship between their structures and pharmacological effects. Herein, we have developed the method to isolate rituximab from plasma in which endogenous IgGs interfere the detection of rituximab, and successfully developed the analytical method with a liquid chromatograph time-of-flight mass spectrometer to detect the structure of rituximab in plasma with errors less than 30 parts per millions. Eight types of carbohydrate chains in rituximab were detected by this method. Interestingly, time-dependent changes in carbohydrate chains such as AAF (G2F and GnGn (G0 were observed in rats, although the amino acids were stable. Additionally, these structural changes were observed via incubation in plasma as in the rat experiment, suggesting that a certain type of enzyme in plasma caused the alterations of the carbohydrate chains. The present analytical methods could clarify the actual pharmacokinetics of therapeutic mAbs, and help to evaluate the interindividual variations in pharmacokinetics and efficacy.

Micro-costing study of rituximab subcutaneous injection versus intravenous infusion in dutch setting

NARCIS (Netherlands)

Mihajlović, J.; Bax, P.; Van Breugel, E.; Blommestein, H.M.; Hoogendoorn, M.; Hospes, W.; Postma, M.J.

2015-01-01

Background: Rituximab for subcutaneous (SC) administration has recently been approved for use in common forms of diffuse large B-cell lymphoma (DLBCL). This form of rituximab is supplied in ready-to-use vials that do not require individual dose adjustment. It is expected that SC-injection will

Analytical similarity assessment of rituximab biosimilar CT-P10 to reference medicinal product.

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Lee, Kyoung Hoon; Lee, Jihun; Bae, Jin Soo; Kim, Yeon Jung; Kang, Hyun Ah; Kim, Sung Hwan; Lee, So Jung; Lim, Ki Jung; Lee, Jung Woo; Jung, Soon Kwan; Chang, Shin Jae

2018-04-01

CT-P10 (Truxima™) was recently approved as the world's first rituximab biosimilar product in the European Union (EU) and South Korea. To demonstrate biosimilarity of CT-P10 with the reference medicinal product (RMP), extensive 3-way similarity assessment has been conducted between CT-P10, EU-Rituximab and US-Rituximab, focusing on the physicochemical and biological quality attributes. A multitude of state-of-the-art analyses revealed that CT-P10 has identical primary and higher order structures compared to the original product. Purity/impurity profiles of CT-P10 measured by the levels of aggregates, fragments, non-glycosylated form and process-related impurities were also found to be comparable with those of RMPs. In terms of the post-translational modification, CT-P10 contains slightly less N-terminal pyro-glutamate variant, which has been known not to affect product efficacy or safety. Oligosaccharide profiling has revealed that, although CT-P10 contains the same conserved glycan species and relative proportion with the RMPs, the content of total afucosylated glycan in CT-P10 was slightly higher than in EU- or US-Rituximab. Nevertheless, the effect of the observed level of afucosylation in CT-P10 drug product on Fc receptor binding affinity or antibody-dependent cell-mediated cytotoxicity was found to be negligible based on the spiking study with highly afucosylated sample. Arrays of biological assays representative of known and putative mechanisms of action for rituximab have shown that biological activities of CT-P10 are within the quality range of RMPs. Recent results of clinical studies have further confirmed that the CT-P10 exhibits equivalent clinical efficacy and safety profiles compared to EU- and US-Rituximab. The current 3-way similarity assessment together with clinical study results confidently demonstrate that CT-P10 is highly similar with EU- and US-Rituximab in terms of physicochemical properties, biological activities, efficacy, and safety for

Long-term safety of rituximab induced peripheral B-cell depletion in autoimmune neurological diseases.

Directory of Open Access Journals (Sweden)

Anza B Memon

Full Text Available B-cells play a pivotal role in several autoimmune diseases, including patients with immune-mediated neurological disorders (PIMND, such as neuromyelitis optica (NMO, multiple sclerosis (MS, and myasthenia gravis (MG. Targeting B-cells has been an effective approach in ameliorating both central and peripheral autoimmune diseases. However, there is a paucity of literature on the safety of continuous B-cell depletion over a long period of time.The aim of this study was to examine the long-term safety, incidence of infections, and malignancies in subjects receiving continuous therapy with a B-cell depleting agent rituximab over at least 3 years or longer.This was a retrospective study involving PIMND who received continuous cycles of rituximab infusions every 6 to 9 months for up to 7 years. The incidence of infection related adverse events (AE, serious adverse events (SAE, and malignancies were observed.There were a total of 32 AE and 4 SAE with rituximab treatment. The 3 SAE were noted after 9 cycles (48 months and 1 SAE was observed after 11 cycles (60 months of rituximab. There were no cases of Progressive multifocal leukoencephalopathy (PML and malignancies observed throughout the treatment period. Rituximab was well tolerated without any serious infusion reactions. Also, rituximab was found to be beneficial in treating PIMND over a 7-year period.This study demonstrates that long-term depletion of peripheral B-cells appears safe and efficacious in treating PIMND. Longer and larger prospective studies with rituximab are needed to carefully ascertain risks associated with chronic B-cell depletion, including malignancies. Recognizing that this is a small, retrospective study, such data nonetheless complement the growing literature documenting the safety and tolerability of B-cell depleting agents in neurological diseases.

Rituximab and Dexamethasone vs Dexamethasone Monotherapy in Newly Diagnosed Patients with Primary Immune Thrombocytopenia

DEFF Research Database (Denmark)

Gudbrandsdottir, Sif; Birgens, Henrik Sverre; Frederiksen, Henrik

2013-01-01

In this study, we report the results from the largest cohort to date of newly diagnosed adult immune thrombocytopenia patients randomized to treatment with dexamethasone alone or in combination with rituximab. Eligible were patients with platelet counts ≤25×10(9)/L or ≤50×10(9)/L with bleeding sy...

Rituximab, alkylating agents or combination therapy for gastric mucosa-associated lymphoid tissue lymphoma: a monocentric non-randomised observational study.

Science.gov (United States)

Amiot, A; Lévy, M; Copie-Bergman, C; Dupuis, J; Szablewski, V; Le Baleur, Y; Baia, M; Belhadj, K; Sobhani, I; Leroy, K; Haioun, C; Delchier, J-C

2014-03-01

There is no consensus on the standard treatment of gastric mucosa-associated lymphoid tissue (MALT) lymphoma for Helicobacter pylori-negative patients and for patients with persistent disease despite H. pylori eradication. To evaluate the comparative efficacy and safety of alkylating agents and rituximab alone or in combination. In this monocentric retrospective study, which included 106 patients who had not been previously treated with anti-cancer agents, we evaluated the efficacy and safety of oral alkylating agents monotherapy (n = 48), rituximab monotherapy (n = 28) and the therapy combining both drugs (n = 30). Evaluations were performed at weeks 6 (W6), 25 (W25), and 52 (W52) and after 2 years (W104). After a median follow-up period of 4.9 years (range 0.4-17.2 years), complete remission and overall response were significantly higher in patients in the combination therapy group at W104 (92% and 100% respectively) compared with patients treated with alkylating agents alone (66% and 68%) and rituximab alone (64% and 73%). The 5-year progression-free survival probabilities were 68%, 70% and 89% in patients treated with alkylating agents alone, rituximab alone and combination therapy respectively. Haematological adverse events were reported in 32 (30%) patients (mostly grade 1) and were more frequent in the two groups receiving alkylating agents (P = 0.05 and P alkylating agents alone. Rituximab has a better safety profile than regimens containing alkylating agents. © 2014 John Wiley & Sons Ltd.

Favourable response to rituximab by an ocular adnexal primary lymphoma.

Science.gov (United States)

Luque Valentin-Fernandez, M L; Alvarez Rodríguez, F; Rodríguez Jiménez, I

2016-11-01

A 70-year-old woman who presented with an extranodal marginal zone B-cell lymphoma in lacrimal gland and conjunctiva. Initial treatment with rituximab yielded an immediate good response. Five months later she showed lymphoid proliferation in her contralateral conjunctiva. Although no additional treatment was performed, the patient has been free of systemic symptoms and recurrences. Rituximab is a quite good therapeutic agent in low grade adnexal lymphomas. Copyright © 2016 Sociedad Española de Oftalmología. Publicado por Elsevier España, S.L.U. All rights reserved.

Imaging and measuring the rituximab-induced changes of mechanical properties in B-lymphoma cells using atomic force microscopy

Energy Technology Data Exchange (ETDEWEB)

Li, Mi [State Key Laboratory of Robotics, Shenyang Institute of Automation, Chinese Academy of Sciences, Shenyang 110016 (China); Graduate University of Chinese Academy of Sciences, Beijing 100049 (China); Liu, Lianqing, E-mail: lqliu@sia.cn [State Key Laboratory of Robotics, Shenyang Institute of Automation, Chinese Academy of Sciences, Shenyang 110016 (China); Xi, Ning, E-mail: xin@egr.msu.edu [State Key Laboratory of Robotics, Shenyang Institute of Automation, Chinese Academy of Sciences, Shenyang 110016 (China); Department of Electrical and Computer Engineering, Michigan State University, East Lansing, MI 48824 (United States); Wang, Yuechao; Dong, Zaili [State Key Laboratory of Robotics, Shenyang Institute of Automation, Chinese Academy of Sciences, Shenyang 110016 (China); Tabata, Osamu [Department of Micro Engineering, Kyoto University, Kyoto 606-8501 (Japan); Xiao, Xiubin [Department of Lymphoma, Affiliated Hospital of Military Medical Academy of Sciences, Beijing 100071 (China); Zhang, Weijing, E-mail: zhangwj3072@163.com [Department of Lymphoma, Affiliated Hospital of Military Medical Academy of Sciences, Beijing 100071 (China)

2011-01-14

Research highlights: {yields} Single B-lymphoma living cells were imaged by AFM with the assistance of microfabricated pillars. {yields} The apoptosis of B-lymphoma cells triggered by rituximab without cross-linking was observed by AO/EB double fluorescent staining. {yields} The B-lymphoma cells became dramatically softer after adding rituximab. -- Abstract: The topography and mechanical properties of single B-lymphoma cells have been investigated by atomic force microscopy (AFM). With the assistance of microfabricated patterned pillars, the surface topography and ultrastructure of single living B-lymphoma cell were visualized by AFM. The apoptosis of B-lymphoma cells induced by rituximab alone was observed by acridine orange/ethidium bromide (AO/EB) double fluorescent staining. The rituximab-induced changes of mechanical properties in B-lymphoma cells were measured dynamically and the results showed that B-lymphoma cells became dramatically softer after incubation with rituximab. These results can improve our understanding of rituximab'effect and will facilitate the further investigation of the underlying mechanisms.

Real world costs and cost-effectiveness of Rituximab for diffuse large B-cell lymphoma patients: a population-based analysis.

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Khor, Sara; Beca, Jaclyn; Krahn, Murray; Hodgson, David; Lee, Linda; Crump, Michael; Bremner, Karen E; Luo, Jin; Mamdani, Muhammad; Bell, Chaim M; Sawka, Carol; Gavura, Scott; Sullivan, Terrence; Trudeau, Maureen; Peacock, Stuart; Hoch, Jeffrey S

2014-08-12

Current treatment of diffuse-large-B-cell lymphoma (DLBCL) includes rituximab, an expensive drug, combined with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) chemotherapy. Economic models have predicted rituximab plus CHOP (RCHOP) to be a cost-effective alternative to CHOP alone as first-line treatment of DLBCL, but it remains unclear what its real-world costs and cost-effectiveness are in routine clinical practice. We performed a population-based retrospective cohort study from 1997 to 2007, using linked administrative databases in Ontario, Canada, to evaluate the costs and cost-effectiveness of RCHOP compared to CHOP alone. A historical control cohort (n = 1,099) with DLBCL who received CHOP before rituximab approval was hard-matched on age and treatment intensity and then propensity-score matched on sex, comorbidity, and histology to 1,099 RCHOP patients. All costs and outcomes were adjusted for censoring using the inverse probability weighting method. The main outcome measure was incremental cost per life-year gained (LYG). Rituximab was associated with a life expectancy increase of 3.2 months over 5 years at an additional cost of $16,298, corresponding to an incremental cost-effectiveness ratio of $61,984 (95% CI $34,087-$135,890) per LYG. The probability of being cost-effective was 90% if the willingness-to-pay threshold was $100,000/LYG. The cost-effectiveness ratio was most favourable for patients less than 60 years old ($31,800/LYG) but increased to $80,600/LYG for patients 60-79 years old and $110,100/LYG for patients ≥ 80 years old. We found that post-market survival benefits of rituximab are similar to or lower than those reported in clinical trials, while the costs, incremental costs and cost-effectiveness ratios are higher than in published economic models and differ by age. Our results showed that the addition of rituximab to standard CHOP chemotherapy was associated with improvement in survival but at a higher cost, and was

A Randomized, Controlled Trial of Rituximab in IgA Nephropathy with Proteinuria and Renal Dysfunction.

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Lafayette, Richard A; Canetta, Pietro A; Rovin, Brad H; Appel, Gerald B; Novak, Jan; Nath, Karl A; Sethi, Sanjeev; Tumlin, James A; Mehta, Kshama; Hogan, Marie; Erickson, Stephen; Julian, Bruce A; Leung, Nelson; Enders, Felicity T; Brown, Rhubell; Knoppova, Barbora; Hall, Stacy; Fervenza, Fernando C

2017-04-01

IgA nephropathy frequently leads to progressive CKD. Although interest surrounds use of immunosuppressive agents added to standard therapy, several recent studies have questioned efficacy of these agents. Depleting antibody-producing B cells potentially offers a new therapy. In this open label, multicenter study conducted over 1-year follow-up, we randomized 34 adult patients with biopsy-proven IgA nephropathy and proteinuria >1 g/d, maintained on angiotensin-converting enzyme inhibitors or angiotensin receptor blockers with well controlled BP and eGFR<90 ml/min per 1.73 m 2 , to receive standard therapy or rituximab with standard therapy. Primary outcome measures included change in proteinuria and change in eGFR. Median baseline serum creatinine level (range) was 1.4 (0.8-2.4) mg/dl, and proteinuria was 2.1 (0.6-5.3) g/d. Treatment with rituximab depleted B cells and was well tolerated. eGFR did not change in either group. Rituximab did not alter the level of proteinuria compared with that at baseline or in the control group; three patients in each group had ≥50% reduction in level of proteinuria. Serum levels of galactose-deficient IgA1 or antibodies against galactose-deficient IgA1 did not change. In this trial, rituximab therapy did not significantly improve renal function or proteinuria assessed over 1 year. Although rituximab effectively depleted B cells, it failed to reduce serum levels of galactose-deficient IgA1 and antigalactose-deficient IgA1 antibodies. Lack of efficacy of rituximab, at least at this stage and severity of IgA nephropathy, may reflect a failure of rituximab to reduce levels of specific antibodies assigned salient pathogenetic roles in IgA nephropathy. Copyright © 2017 by the American Society of Nephrology.

Validation of a treatment satisfaction questionnaire in non-Hodgkin lymphoma: assessing the change from intravenous to subcutaneous administration of rituximab.

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Theodore-Oklota, Christina; Humphrey, Louise; Wiesner, Christof; Schnetzler, Gabriel; Hudgens, Stacie; Campbell, Alicyn

2016-01-01

A subcutaneous (SC) formulation of rituximab (MabThera ® /Rituxan ® ) has been developed that could reduce administration time and improve patient satisfaction with treatment. The Rituximab Administration Satisfaction Questionnaire (RASQ) was created to assess patients' perceptions and satisfaction with rituximab SC (RASQ-SC) or rituximab intravenous (RASQ-IV). We assessed the content validity and psychometric properties of RASQ in patients with non-Hodgkin lymphoma. Face and content validity of RASQ-SC and RASQ-IV were qualitatively assessed using 60-minute combined concept elicitation and cognitive debriefing interviews. Psychometric validation of RASQ (item performance and reliability) was assessed quantitatively against the established Cancer Therapy Satisfaction Questionnaire (CTSQ), using questionnaire data from the PrefMab (NCT01724021) and MabCute (NCT01461928) clinical studies. RASQ-IV demonstrated excellent coverage of concepts relevant to patients' (n=10) own treatment experiences and no new concepts were identified. Patients' expectations of rituximab SC were conceptually consistent with items included in the RASQ-SC, suggesting that the tool is also conceptually adequate. In 1,051 patients from PrefMab and MabCute, correlations with domains such as "RASQ: Physical Impacts" and "CTSQ: Feelings About Side Effects", "RASQ: Physical Impacts" and "CTSQ: Satisfaction With Therapy", and "RASQ: Satisfaction" and "CTSQ: Satisfaction With Therapy", achieved moderate-to-high correlations (>0.4) for convergent domains and <0.3 for divergent domains. This study supports the qualitative face and content validity and psychometric validity of RASQ-IV and RASQ-SC. Minor revisions were made to the questionnaires to enhance clarity and aid consistent reporting.

Off-label use of rituximab in autoimmune disease in the Top End of the Northern Territory, 2008-2016.

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Wongseelashote, Sarah; Tayal, Vipin; Bourke, Peter Francis

2018-02-01

Rituximab, an anti-CD20 B-cell depleting monoclonal antibody, is increasingly prescribed off-label for a range of autoimmune diseases. There has not previously been an audit of off-label rituximab use in the Northern Territory, where the majority of patients are Aboriginal. To evaluate retrospectively off-label rituximab use in autoimmune diseases in the Top End of the Northern Territory. We performed a retrospective audit of 8 years of off-label rituximab use at the Royal Darwin Hospital, the sole tertiary referral centre for the Darwin, Katherine and East Arnhem regions. Electronic and paper records were reviewed for demographic information, diagnosis/indication for rituximab, doses, previous/concomitant immunosuppression, clinical outcomes and specific adverse events. Rituximab was prescribed off-label to 66 patients for 24 autoimmune diseases. The majority of patients (62.1%) were Aboriginal and 60.6% female. The most common indications were refractory/relapsing disease despite standard therapies (68.7%) or severe disease with rituximab incorporated into an induction immunosuppressive regimen (19.4%). Systemic lupus erythematosus was the underlying diagnosis in 28.8% of cases. A clinically significant response was demonstrated in 74.2% of cases overall. There were 18 clinically significant infections; however, 13 were in patients receiving concurrent immunosuppressive therapy. There was a total of nine deaths from any cause. Rituximab has been used off-label for a range of autoimmune diseases in this population with a high proportion of Aboriginal patients successfully and safely in the majority of cases. © 2017 Royal Australasian College of Physicians.

Rituximab in the treatment of primary cutaneous B-cell lymphoma: a review.

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Fernández-Guarino, M; Ortiz-Romero, P L; Fernández-Misa, R; Montalbán, C

2014-06-01

Rituximab is a chimeric mouse-human antibody that targets the CD20 antigen, which is found in both normal and neoplastic B cells. In recent years, it has been increasingly used to treat cutaneous B-cell lymphoma and is now considered an alternative to classic treatment (radiotherapy and surgery) of 2 types of indolent lymphoma, namely, primary cutaneous follicle center lymphoma and primary cutaneous marginal zone B-cell lymphoma. Rituximab is also administered as an alternative to polychemotherapy in the treatment of primary cutaneous large B-cell lymphoma, leg type. Its use as an alternative drug led to it being administered intralesionally, with beneficial effects. In the present article, we review the literature published on the use of rituximab to treat primary cutaneous B-cell lymphoma. Copyright © 2012 Elsevier España, S.L. and AEDV. All rights reserved.

Internalisation of uncross-linked rituximab is not essential for the induction of caspase-independent killing in Burkitt lymphoma cell lines.

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Turzanski, Julie; Daniels, Ian; Haynes, Andrew P

2008-08-01

Characterising the mechanisms underpinning caspase-independent programmed cell death (CI-PCD) induction by uncross-linked rituximab in B-cells may positively impact upon the treatment of disease states in which the classical apoptotic pathway is disabled. The necessity of rituximab internalisation for CI-PCD induction was investigated by flow cytometry and confocal microscopy in human BL cell lines with (e.g. Mutu I) and without (Mutu III) susceptibility to rituximab-induced killing. Flow cytometry demonstrated small, significant and similar amounts of rituximab internalisation by Mutu I cells after 1, 2, 4 and 24 h (p internalisation (p = 0.02, n = 5 and p = 0.0002, n = 6, respectively) in Mutu I cells, but confocal microscopy showed no correlation between internalised rituximab and phosphatidylserine exposure. We conclude that rituximab internalisation is not essential for CI-PCD induction in BL cell lines.

Validation of a treatment satisfaction questionnaire in non-Hodgkin lymphoma: assessing the change from intravenous to subcutaneous administration of rituximab

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Theodore-Oklota C

2016-09-01

Full Text Available Christina Theodore-Oklota,1 Louise Humphrey,2 Christof Wiesner,1 Gabriel Schnetzler,3 Stacie Hudgens,4 Alicyn Campbell1 1Genentech, South San Francisco, CA, USA; 2Adelphi Values, Macclesfield, Cheshire, UK; 3F. Hoffmann La-Roche Ltd, Basel, Switzerland; 4Clinical Outcomes Solutions, Tucson, AZ, USA Background: A subcutaneous (SC formulation of rituximab (MabThera®/Rituxan® has been developed that could reduce administration time and improve patient satisfaction with treatment. The Rituximab Administration Satisfaction Questionnaire (RASQ was created to assess patients’ perceptions and satisfaction with rituximab SC (RASQ-SC or rituximab intravenous (RASQ-IV. We assessed the content validity and psychometric properties of RASQ in patients with non-Hodgkin lymphoma.Methods: Face and content validity of RASQ-SC and RASQ-IV were qualitatively assessed using 60-minute combined concept elicitation and cognitive debriefing interviews. Psychometric validation of RASQ (item performance and reliability was assessed quantitatively against the established Cancer Therapy Satisfaction Questionnaire (CTSQ, using questionnaire data from the PrefMab (NCT01724021 and MabCute (NCT01461928 clinical studies.Results: RASQ-IV demonstrated excellent coverage of concepts relevant to patients’ (n=10 own treatment experiences and no new concepts were identified. Patients’ expectations of rituximab SC were conceptually consistent with items included in the RASQ-SC, suggesting that the tool is also conceptually adequate. In 1,051 patients from PrefMab and MabCute, correlations with domains such as “RASQ: Physical Impacts” and “CTSQ: Feelings About Side Effects”, “RASQ: Physical Impacts” and “CTSQ: Satisfaction With Therapy”, and “RASQ: Satisfaction” and “CTSQ: Satisfaction With Therapy”, achieved moderate-to-high correlations (>0.4 for convergent domains and <0.3 for divergent domains.Conclusion: This study supports the qualitative face and

Ibrutinib, lenalidomide, and rituximab in relapsed or refractory mantle cell lymphoma (PHILEMON)

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Jerkeman, Mats; Eskelund, Christian Winther; Hutchings, Martin

2018-01-01

BACKGROUND: Regimens based on ibrutinib alone and lenalidomide and rituximab in combination show high activity in patients with relapsed or refractory mantle cell lymphoma. We hypothesised that the combination of all three drugs would improve efficacy compared with previously published data...... performance status score of 0-3, and at least one site of measurable disease, and who met criteria for several laboratory-assessed parameters. Treatment was divided into an induction phase of 12 cycles of 28 days with all three drugs and a maintenance phase with ibrutinib and rituximab only (cycle duration 56...... days), given until disease progression or unacceptable toxicity. In the induction phase, patients received intravenous (375 mg/m2) or subcutaneous (1400 mg) rituximab once a week during cycle 1 and then once every 8 weeks. Oral ibrutinib (560 mg once a day) was given to patients every day in the cycle...

Rituximab as a possible cause of posterior reversible encephalopathy syndrome

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Ahmed Imran Siddiqi

2011-09-01

Full Text Available A 66-year-old woman presented with new onset generalisedtonic-clonic seizures following her first dose ofchemotherapy comprising Rituximab, Cyclophosphamide,Hydroxydaunorubicin, Oncovin and Prednisolone (R-CHOP10 days earlier for non-Hodgkin’s lymphoma. On admission,computed tomography (CT scan of the cranium showed noabnormality. The CT was repeated within 48 hours as thepatient developed status epilepticus and papilledema; therepeat scan showed characteristics of posterior reversibleencephalopathy syndrome (PRES. Association of rituximabwith this condition was suspected as there was norecurrence of PRES after receiving two more cycles of CHOPwithout rituximab. Contrary to previously published casereports, this patient had a delayed clinical presentation.

MDM2 phenotypic and genotypic profiling, respective to TP53 genetic status, in diffuse large B-cell lymphoma patients treated with rituximab-CHOP immunochemotherapy: a report from the International DLBCL Rituximab-CHOP Consortium Program

NARCIS (Netherlands)

Xu-Monette, Z.Y.; Moller, M.B.; Tzankov, A.; Montes-Moreno, S.; Hu, W.; Manyam, G.C.; Kristensen, L.; Fan, L.; Visco, C.; Dybkaer, K.; Chiu, A.; Tam, W.; Zu, Y.; Bhagat, G.; Richards, K.L.; Hsi, E.D.; Choi, W.W.; Krieken, J.H.J.M. van; Huang, Q.; Huh, J.; Ai, W.; Ponzoni, M.; Ferreri, A.J.; Wu, L.; Zhao, X.; Bueso-Ramos, C.E.; Wang, S.A.; Go, R.S.; Li, Y.; Winter, J.N.; Piris, M.A.; Medeiros, L.J.; Young, K.H.

2013-01-01

MDM2 is a key negative regulator of the tumor suppressor p53, however, the prognostic significance of MDM2 overexpression in diffuse large B-cell lymphoma (DLBCL) has not been defined convincingly. In a p53 genetically-defined large cohort of de novo DLBCL patients treated with rituximab,

B cells and immunoglobulin in ABO-incompatible renal transplant patients receiving rituximab and double filtration plasmapheresis

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Meng-Kun Tsai

2015-04-01

Conclusion: With the aid of tacrolimus and mycophenolate mofetil, rituximab resulted in sustained suppression of B cell count and total IgG and IgM. Among the IgG subclasses, IgG3 was less sensitive to rituximab.

{sup 99m}Tc-rituximab radiolabelled by photo-activation: a new non-Hodgkin's lymphoma imaging agent

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Gmeiner Stopar, T.; Fettich, J.; Hojker, S. [University Medical Centre Ljubljana, Department for Nuclear Medicine, Ljubljana (Slovenia); Mlinaric-Rascan, I. [University of Ljubljana, Faculty of Pharmacy, Ljubljana (Slovenia); Mather, S.J. [St Bartholomew' s Hospital, Cancer Research UK, Department Nuclear Medicine, London (United Kingdom)

2006-01-01

Rituximab was the first chimeric monoclonal antibody to be approved for treatment of indolent B-cell non-Hodgkin's lymphoma (NHL). It is directed against the CD20 antigen, which is expressed by 95% of B-cell NHLs. The aim of this study was to explore the possibility of radiolabelling rituximab with {sup 99m}Tc for use as an imaging agent in NHL for early detection, staging, remission assessment, monitoring for metastatic spread and tumour recurrence, and assessment of CD20 expression prior to (radio)immunotherapy. Rituximab was purified from Mabthera solution (Roche), photo-activated at 302 nm by UV irradiation and radiolabelled with {sup 99m}Tc. The effectiveness of the labelling method was evaluated by determination of the number of free thiol groups per photoreduced antibody, radiochemical purity and in vitro stability of {sup 99m}Tc-rituximab. On average, 4.4 free thiol groups per photoreduced antibody were determined. Radiolabelling yields greater than 95% were routinely observed after storage of the photo-activated antibody at -80 C for 195 days. The direct binding assay showed preserved ability of {sup 99m}Tc-rituximab to bind to CD20, with an average immunoreactive fraction of 93.3%. The internalisation rate was proven to be low, with only 5.3% of bound {sup 99m}Tc-rituximab being internalised over 4 h at 37 C. Our results demonstrate that {sup 99m}Tc-rituximab of high radiochemical purity and with preserved binding affinity for the antigen can be prepared by photoreduction and that the method shows good reproducibility. {sup 99m}Tc-rituximab will be further explored as an imaging agent applicable in NHL for the purposes mentioned above. (orig.)

Rituximab as maintenance therapy for ANCA associated vasculitis: how, when and why?

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Alba, Marco A; Flores-Suárez, Luis Felipe

2016-01-01

ANCA-associated vasculitides (AAV) are chronic autoimmune diseases characterized by inflammation and destruction of small vessels. Rituximab is now licensed for use as a remission-induction agent in the treatment of these disorders. During recent years, several non-controlled studies have suggested that rituximab may be of value in maintaining disease remission in AAV. In these series, 3 techniques have been tried: "watch-and-wait", repeated cycles in fixed intervals, or administration based on proposed biomarkers. More importantly, the results of the MAINRITSAN trial showed that this anti-CD20 agent is superior to azathioprine for preventing major relapses in AAV. This review summarizes current information regarding the effectiveness, timing, dosing, duration and safety of rituximab as a valid option for remission maintenance. Copyright © 2015 Elsevier España, S.L.U. y Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.

In Vitro Cytotoxicity of Low-Dose-Rate Radioimmunotherapy by the Alpha-Emitting Radioimmunoconjugate Thorium-227-DOTA-Rituximab

International Nuclear Information System (INIS)

Dahle, Jostein; Krogh, Cecilie; Melhus, Katrine B.; Borrebaek, Jorgen; Larsen, Roy H.; Kvinnsland, Yngve

2009-01-01

Purpose: To determine whether the low-dose-rate α-particle-emitting radioimmunoconjugate 227 Th-1,4,7,10-p-isothiocyanato-benzyl-tetraazacyclododecane-1,4,7, 10-tetraacetic acid (DOTA)-rituximab can be used to inactivate lymphoma cells growing as single cells and small colonies. Methods and Materials: CD20-positive lymphoma cell lines were treated with 227 Th-DOTA-rituximab for 1-5 weeks. To simulate the in vivo situation with continuous but decreasing supply of radioimmunoconjugates from the blood pool, the cells were not washed after incubation with 227 Th-DOTA-rituximab, but half of the medium was replaced with fresh medium, and cell concentration and cell-bound activity were determined every other day after start of incubation. A microdosimetric model was established to estimate the average number of hits in the nucleus for different localizations of activity. Results: There was a specific targeted effect on cell growth of the 227 Th-DOTA-rituximab treatment. Although the cells were not washed after incubation with 227 Th-DOTA-rituximab, the average contribution of activity in the medium to the mean dose was only 6%, whereas the average contribution from activity on the cells' own surface was 78%. The mean dose rates after incubation with 800 Bq/mL 227 Th-DOTA-rituximab varied from 0.01 to 0.03 cGy/min. The average delay in growing from 10 5 to 10 7 cells/mL was 15 days when the cells were treated with a mean absorbed radiation dose of 2 Gy α-particle radiation from 227 Th-DOTA-rituximab, whereas it was 11 days when the cells were irradiated with 6 Gy of X-radiation. The relative biologic effect of the treatment was estimated to be 2.9-3.4. Conclusions: The low-dose-rate radioimmunoconjugate 227 Th-DOTA-rituximab is suitable for inactivation of single lymphoma cells and small colonies of lymphoma cells.

Interferon-regulated chemokine score associated with improvement in disease activity in refractory myositis patients treated with rituximab.

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López De Padilla, Consuelo M; Crowson, Cynthia S; Hein, Molly S; Strausbauch, Michael A; Aggarwal, Rohit; Levesque, Marc C; Ascherman, Dana P; Oddis, Chester V; Reed, Ann M

2015-01-01

The purpose of this study was to investigate whether serum interferon (IFN)-regulated chemokine and distinct cytokine response profiles are associated with clinical improvement in patients with refractory inflammatory myopathy treated with rituximab. In a randomised, placebo-phase trial Rituximab in Myositis Trial (RIM), 200 refractory adult and paediatric myositis subjects received rituximab. Following rituximab, clinical response and disease activity were assessed. Serum samples and clinical data were collected at baseline and several time-points after rituximab treatment. Multiplexed sandwich immunoassays quantified serum levels of IFN-regulated chemokines and other pro-inflammatory cytokines. Composite IFN-regulated chemokine and Th1, Th2, Th17 and regulatory cytokine scores were computed. Baseline IFN-regulated chemokine, Th1, Th2, Th17 and regulatory cytokine scores correlated with baseline physician global VAS, whereas the baseline Th1, Th2 and Th17 cytokine scores correlated with baseline muscle VAS. We also found baseline IFN-regulated chemokine scores correlated with specific non-muscular targets such as baseline cutaneous (r=0.29; p=0.002) and pulmonary (r=0.18; p=0.02) VAS scores. Among all cytokine/chemokines examined, the baseline score of IFN-regulated chemokines demonstrated the best correlation with changes in muscle VAS at 8 (r=-0.19; p=0.01) and 16 weeks (r=-0.17; p=0.03) following rituximab and physician global VAS at 16 weeks (r=-0.16; p=0.04). In vitro experiments showed increased levels of IL-8 (p=0.04), MCP-1 (p=0.04), IL-6 (p=0.03), IL-1β (p=0.04), IL-13 (p=0.04), IL-10 (p=0.02), IL-2 (p=0.04) and IFN-γ (p=0.02) in supernatants of TLR-3 stimulated PBMCs from non-responder compared to patients responders to rituximab. IFN-regulated chemokines before treatment is associated with improvement in disease activity measures in refractory myositis patients treated with rituximab.

A phase III randomized trial comparing glucocorticoid monotherapy versus glucocorticoid and rituximab in patients with autoimmune haemolytic anaemia

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Birgens, Henrik Sverre; Frederiksen, Henrik; Hasselbalch, Hans C

2013-01-01

The impact of first-line treatment with the anti-CD 20 chimeric monoclonal antibody rituximab in patients with warm-antibody reactive autoimmune haemolytic anaemia (WAIHA) is unknown. We report the first randomized study of 64 patients with newly diagnosed WAIHA who received prednisolone and ritu...

Medical resource utilization in dermatomyositis/polymyositis patients treated with repository corticotropin injection, intravenous immunoglobulin, and/or rituximab

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Knight T

2017-05-01

Full Text Available Tyler Knight,1 T Christopher Bond,1 Breanna Popelar,2 Li Wang,3 John W Niewoehner,4 Kathryn Anastassopoulos,1 Michael Philbin4 1Covance Market Access Services Inc., Gaithersburg, MD, 2Xcenda, LLC, Palm Harbor, FL, 3STATinMED Research, Ann Arbor, MI, 4Mallinckrodt, LLC, Hazelwood, MO, USA Background: Dermatomyositis and polymyositis (DM/PM are rare, incurable inflammatory diseases that cause progressive muscle weakness and can be associated with increased medical resource use (MRU. When corticosteroid treatment is unsuccessful, patients may receive intravenous immunoglobulin (IVIg, rituximab, or repository corticotropin injection (RCI. This study compared real-world, non-medication MRU between patients treated with RCI and those treated with IVIg and/or rituximab for DM/PM.Methods: Claims of DM/PM patients were analyzed from the combination of three commercial health insurance databases in the United States from July 2009 to June 2014. Patients treated with RCI were propensity score matched to those treated with IVIg, rituximab, and both (IVIg+rituximab based on demographics, prior clinical characteristics, and prior MRU. Per-patient per-month (PPPM MRU and costs were compared using Poisson regression and generalized linear modeling, respectively.Results: One-hundred thirty-two RCI, 1,150 IVIg, and 562 rituximab patients had an average age of 52.6, 46.6, and 51.7 years, respectively, and roughly two-thirds were female. After matching, there were no significant differences in demographics or prior clinical characteristics. RCI patients had fewer PPPM hospitalizations (0.09 vs 0.17; P=0.049, shorter length of stay (LOS; 3.24 days vs 4.55 days; P=0.004, PPPM hospital outpatient department (HOPD visits (0.60 vs 1.39; P<0.001, and PPPM physician office visits (2.01 vs 2.33; P=0.035 than IVIg. RCI had fewer PPPM HOPD visits (0.56 vs 0.92; P<0.001 than rituximab. Patients treated with RCI had shorter LOS (2.18 days vs 5.15; P<0.001 and less PPPM HOPD

Novel use of rituximab in a case of Riedel's thyroiditis refractory to glucocorticoids and tamoxifen.

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Soh, Shui-Boon; Pham, Alan; O'Hehir, Robyn E; Cherk, Martin; Topliss, Duncan J

2013-09-01

A 42-year-old woman presented with a rapidly enlarging right-sided thyroid mass and underwent hemithyroidectomy. Riedel's thyroiditis was only diagnosed upon surgical decompression of the right carotid artery 2 years later. She became more symptomatic as Riedel's thyroiditis progressed, and mediastinal fibrosclerosis developed over the next 12 months. Oral prednisolone failed to improve her condition, and she was commenced on tamoxifen. Despite initial improvement, her symptoms recurred 2 years later, mainly arising from compression of the trachea and esophagus at the thoracic inlet. Fluorodeoxyglucose positron emission tomographic scan showed locally advanced active invasive fibrosclerosis in the neck and mediastinum. An elevated activin-A level of 218 pg/mL was consistent with active inflammation. IgG subtypes (including IgG4) were normal. Two courses of iv methylprednisolone were given but only produced transient improvement. Subsequently, the patient received 3 doses of i.v. rituximab at monthly intervals and had prompt sustained symptomatic improvement. Activin-A level decreased to 122 pg/mL 10 months after rituximab therapy. Fluorodeoxyglucose positron emission tomographic scan 6 weeks after therapy showed reduction in inflammation. A further scan at 10 months demonstrated ongoing response to rituximab. This is a case of refractory Riedel's thyroiditis with symptomatic, biochemical, and radiological improvement that has persisted 14 months after rituximab. The likelihood and duration of response to rituximab in Riedel's thyroiditis requires further study.

Clinical and economic aspects of the use of rituximab in non-Hodgkin's lymphoma

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Camila Bezerra Melo Figueirêdo

2014-09-01

Full Text Available Non-Hodgkin's lymphoma (NHL consists of a group of neoplasias involving mainly B cells and represents 90% of all lymphomas. The current available therapy is based on chemotherapy associated with the monoclonal antibody rituximab (Mab Thera(r, which targets the CD20 protein, present in over 80% of NHL mature B cells. Recent clinical reports show a preference for combining the benefits of immunotherapy and adjuvant chemotherapy, thus generating safe and effective alternative treatments. The current review aimed at evaluating various aspects related to the use of rituximab for NHL, highlighting the possible inhibitory mechanisms of cell proliferation, the achieved clinical results, and the expected clinical and economic outcomes of treatments. The results from clinical tests indicate the need for a better understanding of the critical mechanisms of action of this antibody, which may maximize its therapeutic efficacy. This therapy not only represents a viable option to treat most types of NHLs, especially when associated with conventional chemotherapy, but also offers cost-utility and cost-effectiveness advantages.

Absolute lymphocyte count predicts response to rituximab-containing salvage treatment for relapsed/refractory B-cell non-Hodgkin's lymphoma with prior rituximab exposure

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Man-Hsin Hung

2013-04-01

Conclusion: Our study results show that for patients with relapsed/refractory B-cell NHL, rituximab-containing salvage treatment is feasible and generally tolerable. A high ALC-R value was significantly associated with a better response to this treatment.

Mitomycin-C-Induced TTP/HUS Treated Successfully with Rituximab: Case Report and Review of the Literature

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Gunjan Shah

2013-01-01

Full Text Available Microangiopathic hemolytic anemia (MAHA, thrombocytopenia, fever, renal failure, and neurologic symptoms comprise the cardinal features of thrombotic thrombocytopenic purpura and hemolytic uremic syndrome. Etiologies can include medications, infections, cancers, or transplantation. We present a patient with a history of rectal cancer treated with mitomycin-C who developed MAHA, acute kidney injury, and thrombocytopenia 6 months after completing therapy and to did not respond the plasmapheresis or steroids. She was treated with four weekly doses of rituximab with full recovery.

Preclinical safety, pharmacokinetics, pharmacodynamics, and biodistribution studies with Ad35K++ protein: a novel rituximab cotherapeutic

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Maximilian Richter

2016-01-01

Full Text Available Rituximab is a mouse/human chimeric monoclonal antibody targeted toward CD20. It is efficient as first-line therapy of CD20-positive B-cell malignancies. However, a large fraction of treated patients relapse with rituximab-resistant disease. So far, only modest progress has been made in treatment options for rituximab refractory patients. One of the mechanisms for rituximab resistance involves the upregulation of CD46, which is a key cell surface protein that blocks the activation of complement. We have recently developed a technology that depletes CD46 from the cell surface and thereby sensitizes tumor cells to complement-dependent cytotoxicity. This technology is based on a small recombinant protein, Ad35K++ that binds with high affinity to CD46. In preliminary studies using a 6 × histidinyl tagged protein, we had demonstrated that intravenous Ad35K++ injection in combination with rituximab was safe and increased rituximab-mediated killing of CD20-positive target cells in mice and nonhuman primates (NHPs. The presence of the tag, while allowing for easy purification by Ni-NTA chromatography, has the potential to increase the immunogenicity of the recombinant protein. For clinical application, we therefore developed an Ad35K++ protein without His-tag. In the present study, we performed preclinical studies in two animal species (mice and NHPs with this protein demonstrating its safety and efficacy. These studies estimated the Ad35K++ dose range and treatment regimen to be used in patients. Furthermore, we showed that intravenous Ad35K++ injection triggers the shedding of the CD46 extracellular domain in xenograft mouse tumor models and in macaques. Shed serum CD46 can be measured in the serum and can potentially be used as a pharmacodynamic marker for monitoring Ad35K++ activity in patient undergoing treatment with this agent. These studies create the basis for an investigational new drug application for the use of Ad35K++ in combination with

Effect of baseline rheumatoid factor and anticitrullinated peptide antibody serotype on rituximab clinical response: a meta-analysis

NARCIS (Netherlands)

Isaacs, John D.; Cohen, Stanley B.; Emery, Paul; Tak, Paul P.; Wang, Jianmei; Lei, Guiyuan; Williams, Sarah; Lal, Preeti; Read, Simon J.

2013-01-01

Studies examining the relationship between serological status (rheumatoid factor and/or anticitrullinated antibody) and rituximab treatment outcome in rheumatoid arthritis (RA) have been hampered by limited numbers of seronegative patients. To carry out a meta-analysis of trials from the rituximab

Malignant lymphoma of the vagina successfully treated with rituximab, adryamicin, cyclophosphamide, vincristine sulfate, and prednisolone.

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Nasu, K; Okamoto, M; Nishida, M; Takai, N; Narahara, H

2012-01-01

Primary malignant lymphoma of the vagina is extremely rare. The most common histologic subtype is diffuse large B-cell lymphoma (DLBCL). We report a case of vaginal DLBCL successfully treated with chemotherapy consisting of rituximab, adryamicin, cyclophosphamide, vincristine sulfate, and prednisolone (R-CHOP), followed by pelvic irradiation. A 44-year-old Japanese woman was admitted complaining of atypical genital bleeding and puruloid vaginal discharge. Gynecological examination showed an ulceration of the vaginal wall and a hard mass the size of a goose egg beneath the left vaginal wall, which had infiltrated to the left pelvic wall. The pathological diagnosis based on a punch biopsy taken from the vaginal tumor was non-Hodgkin's lymphoma. Based on immunohistochemical study, the tumor was subclassified as activated B-cell type DLBCL. The patient was diagnosed with Ann Arbor Stage IEA DLBCL and Stage III vaginal cancer, according to the International Federation of Gynecologists and Obstetricians (FIGO) classification system. She was successfully treated by six courses of R-CHOP, followed by radiation therapy. The patient is well without evidence of disease 13 months following the initial treatment. Little attention has been paid to the use of rituximab in addition to conventional chemotherapy and the importance of clinical and morphological subgrouping of DLBCL arising in the vagina. The present case indicates that the effects of rituximab on the prognosis of vaginal DLBCL must be evaluated, and that clinical use of immunophenotypic subgrouping should be considered for vaginal DLBCL.

The identification of irreversible rituximab-resistant lymphoma caused by CD20 gene mutations

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Mishima, Y [Department of Clinical Chemotherapy, Cancer Chemotherapy Center, Japanese Foundation for Cancer Research, Tokyo (Japan); Olympas Bio-Imaging Lab, Cancer Chemotherapy Center, Japanese Foundation for Cancer Research, Tokyo (Japan); Terui, Y [Department of Clinical Chemotherapy, Cancer Chemotherapy Center, Japanese Foundation for Cancer Research, Tokyo (Japan); Takeuchi, K [Division of Pathology, Cancer Institute, Japanese Foundation for Cancer Research, Tokyo (Japan); Matsumoto-Mishima, Y; Matsusaka, S [Department of Clinical Chemotherapy, Cancer Chemotherapy Center, Japanese Foundation for Cancer Research, Tokyo (Japan); Utsubo-Kuniyoshi, R [Department of Clinical Chemotherapy, Cancer Chemotherapy Center, Japanese Foundation for Cancer Research, Tokyo (Japan); Olympas Bio-Imaging Lab, Cancer Chemotherapy Center, Japanese Foundation for Cancer Research, Tokyo (Japan); Hatake, K [Department of Clinical Chemotherapy, Cancer Chemotherapy Center, Japanese Foundation for Cancer Research, Tokyo (Japan)

2011-04-01

C-terminal mutations of CD20 constitute part of the mechanisms that resist rituximab therapy. Most CD20 having a C-terminal mutation was not recognized by L26 antibody. As the exact epitope of L26 has not been determined, expression and localization of mutated CD20 have not been completely elucidated. In this study, we revealed that the binding site of L26 monoclonal antibody is located in the C-terminal cytoplasmic region of CD20 molecule, which was often lost in mutated CD20 molecules. This indicates that it is difficult to distinguish the mutation of CD20 from under expression of the CD20 protein. To detect comprehensive CD20 molecules including the resistant mutants, we developed a novel monoclonal antibody that recognizes the N-terminal cytoplasm region of CD20 molecule. We screened L26-negative cases with our antibody and found several mutations. A rituximab-binding analysis using the cryopreserved specimen that mutation was identified in CD20 molecules indicated that the C-terminal region of CD20 undertakes a critical role in presentation of the large loop in which the rituximab-binding site locates. Thus, combination of antibodies of two kinds of epitope permits the identification of C-terminal CD20 mutations associated with irreversible resistance to rituximab and may help the decision of the treatment strategy.

Development and biological studies of ¹⁷⁷Lu-DOTA-rituximab for the treatment of Non-Hodgkin's lymphoma.

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Massicano, Adriana V F; Pujatti, Priscilla B; Alcarde, Lais F; Suzuki, Miriam F; Spencer, Patrick J; Araújo, Elaine B

2016-01-01

The optimization of DOTA-NHS-ester conjugation to Rituximab using different Ab:DOTA molar ratios (1:10, 1:20, 1:50 and 1:100) was studied. High radiochemical yield, in vitro stability and immunoreactive fraction were obtained for the Rituximab conjugated at 1:50 molar ratio, resulting in the incorporation of an average number of 4.9 ± 1.1 DOTA per Rituximab molecule. Labeling with 177Lu was performed in high specific activity with great in vitro stability. Biodistribution in healthy and xenographed mice showed tumor uptake and high in vivo stability as evidenced by low uptake in bone. The properties of 177Lu-DOTA-Rituximab prepared from DOTA-NHS-ester suggest the potential for the application of the 177Lu-labeled antibody in preliminary clinical studies.

Enhanced CDC of B cell chronic lymphocytic leukemia cells mediated by rituximab combined with a novel anti-complement factor H antibody.

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Mark T Winkler

Full Text Available Rituximab therapy for B cell chronic lymphocytic leukemia (B-CLL has met with mixed success. Among several factors to which resistance can be attributed is failure to activate complement dependent cytotoxicity (CDC due to protective complement regulatory proteins, including the soluble regulator complement factor H (CFH. We hypothesized that rituximab killing of non-responsive B-CLL cells could be augmented by a novel human monoclonal antibody against CFH. The B cells from 11 patients with B-CLL were tested ex vivo in CDC assays with combinations of CFH monoclonal antibody, rituximab, and a negative control antibody. CDC of rituximab non-responsive malignant B cells from CLL patients could in some cases be augmented by the CFH monoclonal antibody. Antibody-mediated cytotoxicity of cells was dependent upon functional complement. In one case where B-CLL cells were refractory to CDC by the combination of rituximab plus CFH monoclonal antibody, additionally neutralizing the membrane complement regulatory protein CD59 allowed CDC to occur. Inhibiting CDC regulatory proteins such as CFH holds promise for overcoming resistance to rituximab therapy in B-CLL.

Cyclophosphamide-refractory scleroderma-associated interstitial lung disease: remarkable clinical and radiological response to a single course of rituximab combined with high-dose corticosteroids.

LENUS (Irish Health Repository)

Haroon, Muhammad

2011-10-01

We would like to report our experience of using rituximab in cyclophosphamide refractory, rapidly progressive interstitial lung disease (ILD) in a patient with limited scleroderma. A 40-year-old man presented with 10-week history of inflammatory polyarthritis, which responded to a short course of oral corticosteroids. However, 3 weeks later, he developed new onset of exertional dyspnoea. High-resolution CT of the thorax was suggestive of early ILD. Surgical lung biopsy showed features of fibrotic non-specific interstitial pneumonia. He was diagnosed with scleroderma on the basis of: presence of anticentromere antibodies, Raynaud\\'s phenomenon, pulmonary fibrosis, digital oedema and hypomotility along with a dilated oesophagus. He was treated aggressively with pulse doses of corticosteroids and cyclophosphamide; however, his ILD continued to deteriorate. At this stage, he received rituximab (two pulses of 1 g each), which led to a gradual clinical improvement. Now, 12 months since his rituximab infusion, he walks 2 miles daily without any exertional dyspnoea.

Macroglobulinemia de Waldenström - remissão completa após tratamento com rituximabe Successful outcome in Waldenström's macroglobulinemia treated with rituximab

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Flavia C. F. Pimenta

2008-10-01

blood. Waldenström's macroglobulinemia presents hypergammaglobulinemia with a monoclonal peak of serum proteins seen by electrophoresis, high IgM levels and other normal or diminished immunoglobulin levels, immunophenotyping with CD19+, CD20+ and CD24+ B lymphocytes aspirated from hypercellular bone marrow and hypercellular bone marrow biopsy with diffuse infiltration of lymphocytes, plasmocytoid lymphocytes and plasmocytes. Currently, monoclonal antibodies are successfully being used in the treatment of Waldenström's macroglobulinemia. Rituximab, an anti-CD20 monoclonal antibody, has shown excellent results in the treatment of Waldenström's macroglobulinemia even for individuals who did not obtain satisfactory responses to conventional treatment. This work reports the case of a 78-year-old woman with a history of fatigue, asthenia, anorexia, somnolence, restlessness, urticaria, difficulties in walking, and excessive weight loss (approximately 22 Kg within a period of 5 months who was successfully treated using rituximab. The objective of this report is to present the case of this patient and to review current clinical and therapeutic aspects of the disease.

Rituximab does not reset defective early B cell tolerance checkpoints

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Chamberlain, Nicolas; Massad, Christopher; Oe, Tyler; Cantaert, Tineke; Herold, Kevan C.; Meffre, Eric

2015-01-01

Type 1 diabetes (T1D) patients show abnormalities in early B cell tolerance checkpoints, resulting in the accumulation of large numbers of autoreactive B cells in their blood. Treatment with rituximab, an anti-CD20 mAb that depletes B cells, has been shown to preserve β cell function in T1D patients and improve other autoimmune diseases, including rheumatoid arthritis and multiple sclerosis. However, it remains largely unknown how anti–B cell therapy thwarts autoimmunity in these pathologies. Here, we analyzed the reactivity of Abs expressed by single, mature naive B cells from 4 patients with T1D before and 52 weeks after treatment to determine whether rituximab resets early B cell tolerance checkpoints. We found that anti–B cell therapy did not alter the frequencies of autoreactive and polyreactive B cells, which remained elevated in the blood of all patients after rituximab treatment. Moreover, the limited proliferative history of autoreactive B cells after treatment revealed that these clones were newly generated B cells and not self-reactive B cells that had escaped depletion and repopulated the periphery through homeostatic expansion. We conclude that anti–B cell therapy may provide a temporary dampening of autoimmune processes through B cell depletion. However, repletion with autoreactive B cells may explain the relapse that occurs in many autoimmune patients after anti–B cell therapy. PMID:26642366

Treatment of rheumatoid arthritis with biologic DMARDS (Rituximab and Etanercept).

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Gashi, Afrim A; Rexhepi, Sylejman; Berisha, Idriz; Kryeziu, Avni; Ismaili, Jehona; Krasniqi, Gezim

2014-01-01

To determine efficacy and safety of treatment with Rituximab and Etanercept plus Methotrexate in patients with active Rheumatoid Arthritis (RA), who had an inadequate response to nonbiologic DMARDS therapies and to explore the pharmacogenetics and pharmacodynamics of Rituximab and Etanercept in our populations. Study was done at Rheumatology Clinic of University Clinical Centre in Prishtina during 2009-2011 years. We evaluated primary efficacy and safety at 24 weeks in patients enrolled in the study of long-term efficacy of Rituximab and Etanercept. Patients with active Rheumatoid Arthritis and an inadequate response to 1 or more non biologic DMARDS were randomized to receive intravenous Rituximab (1 course consisting of 2 infusions of 1.000 mg each -one group, and Etanercept 25 mg twice weekly -second group, but both groups with background MTX. The primary efficacy end point was a response on the ACR 20%, improvement criteria at 24 weeks, Secondary end points were responses on the ACR 50 and ACR 70, improvement criteria, the DAS 28, and EULAR response criteria at 24 weeks. During our investigations we treated 20 patients, 15 females and 5 males, in the treated group with RTX and 13 patients 8 females and 5 males in the treated group with ETN. Patients of group 1 and group 2 were of ages 37-69 years old and 19-69 years old (average 47-44) Most of the patients belong in 2nd and 3rd functional stage according to Steinbrocker. All ACR response parameters were significantly improved in RTX treated patients who also had clinically meaningful improvement in fatigue, disability and quality of life. Patients showed a trend less progression in radiographic end points. Most adverse events occurred with the first RTX infusion and were mild to moderate severity. At 24 weeks, a single course of RTX and ETN provided significant and clinically meaningful improvements in disease activity in patients with active, longstanding RA who had an inadequate response to 1 or more

A Multicenter Randomized Controlled Trial of Rituximab versus Cyclosporine in the Treatment of Idiopathic Membranous Nephropathy (MENTOR).

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Fervenza, Fernando C; Canetta, Pietro A; Barbour, Sean J; Lafayette, Richard A; Rovin, Brad H; Aslam, Nabeel; Hladunewich, Michelle A; Irazabal, Maria V; Sethi, Sanjeev; Gipson, Debbie S; Reich, Heather N; Brenchley, Paul; Kretzler, Matthias; Radhakrishnan, Jai; Hebert, Lee A; Gipson, Patrick E; Thomas, Leslie F; McCarthy, Ellen T; Appel, Gerald B; Jefferson, J Ashley; Eirin, Alfonso; Lieske, John C; Hogan, Marie C; Greene, Eddie L; Dillon, John J; Leung, Nelson; Sedor, John R; Rizk, Dana V; Blumenthal, Samuel S; Lasic, Lada B; Juncos, Luis A; Green, Dollie F; Simon, James; Sussman, Amy N; Philibert, David; Cattran, Daniel C

2015-01-01

Idiopathic membranous nephropathy remains the leading cause of nephrotic syndrome in Caucasian adults. Immunosuppressive therapy with cyclosporine (CSA) is often successful in reducing proteinuria, but its use is associated with a high relapse rate. Rituximab, a monoclonal antibody that specifically targets CD20 on the surface of B-cells, is effective in achieving a complete remission of proteinuria in patients with idiopathic membranous nephropathy. However, whether rituximab is as effective as CSA in inducing and maintaining complete or partial remission of proteinuria in these patients is unknown. The membranous nephropathy trial of rituximab (MENTOR) hypothesizes that B-cell targeting with rituximab is non-inferior to CSA in inducing long-term remission of proteinuria. Patients with idiopathic membranous nephropathy, proteinuria ≥5 g/24 h, and a minimum of 3 months of Angiotensin-II blockade will be randomized into a 12-month treatment period with i.v. rituximab, 1,000 mg (2 infusions, 14 days apart; repeated at 6 months if a substantial reduction in proteinuria (equal to or >25%) is seen at 6 months) or oral CSA 3.5-5 mg/kg/day for 6 months (continued for another 6 months if a substantial reduction in proteinuria (equal to or >25%) is seen at 6 months). The efficacy of treatment will be assessed by the remission status (based on changes in proteinuria) at 24 months from randomization. Patient safety will be assessed via collection of adverse event data and evaluation of pre- and posttreatment laboratory data. At the 6-month post-randomization visit, patients who have been randomized to either CSA or rituximab but who do not have a reduction in proteinuria ≥25% (confirmed on repeat measurements within 2 weeks) will be considered treatment failures and exit the study. This study will test for the first time whether treatment with rituximab is non-inferior to CSA in inducing long-term remission (complete or partial) of proteinuria in patients with idiopathic

Testing of mechanisms of action of rituximab and clinical results in high-risk patients with aggressive CD20+ lymphoma

International Nuclear Information System (INIS)

Jezersek Novakovic, B.; Juznic Setina, T.; Vovk, M.; Kotnik, V.; Novakovic, S.

2007-01-01

Rituximab has been applied successfully in the treatment of indolent and aggressive CD20 positive B cell lymphomas, yet the exact in vivo mechanisms of its action have not been unambiguously explained. This study was therefore aimed to confirm the presumed major mechanisms of action of rituximab and concomitantly to assess the effectiveness of first-line chemo immunotherapy in high-risk patients with aggressive CD20 lymphomas. The activity of rituximab was tested in vitro on Raji and SU-DHL-4 cells using the cell proliferation assay and flow cytometry. In the clinical part of the study, 20 high-risk patients with aggressive CD 20 lymphomas were treated with R-CHOP. Only complement-mediated cytotoxicity was observed under the in vitro applied experimental conditions. Neither the direct apoptotic effect nor the antibody-dependent cell-mediated cytotoxicity was detected probably due to a too low concentration of rituximab and a too low ratio of cytotoxic lymphocytes to tumor cells. The treatment outcome in patients was excellent since complete remissions were achieved in 90% of poor-risk patients at the end of primary treatment and 80% of patients were disease-free at 18.5 months median observation period. According to our results, the complement-dependent cytotoxicity is an important mechanism of rituximab action in vitro. To achieve direct apoptosis, higher concentrations than 20 μg/ml of rituximab should be used, while for an effective antibody-dependent cell-mediated cytotoxicity, the ratio of cytotoxic lymphocytes to tumor cells should be higher than 1:1. In the high-risk patients with aggressive CD20 lymphomas, the addition of rituximab to CHOP substantially improves the therapeutic results. (author)

Cost-Effectiveness Analysis of Bendamustine Plus Rituximab as a First-Line Treatment for Patients with Follicular Lymphoma in Spain.

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Sabater, Eliazar; López-Guillermo, Armando; Rueda, Antonio; Salar, Antonio; Oyagüez, Itziar; Collar, Juan Manuel

2016-08-01

Follicular lymphoma (FL) is the second most common type of lymphoid cancer in Western Europe. The aim of this study was to evaluate the cost utility of rituximab-bendamustine treatment compared with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone) treatment as a first-line therapy for patients with advanced FL in Spain. A Markov model was developed to estimate the cost effectiveness of rituximab-bendamustine compared with R-CHOP as first-line treatment for patients with advanced FL in the Spanish National Health System (NHS). Transitions between health states (progression-free, including induction and maintenance; first relapse; second relapse; and death) were allowed for the patient cohort in 4-week-long cycles. Clinical data for the extrapolation of progression-free survival curves were obtained from randomized trials. Mortality rates and utilities were obtained from the literature. Outcomes were measured as quality-adjusted life-years (QALYs). The total costs (€, 2013) included drug costs (ex-factory prices with mandatory deductions), disease management costs and adverse event-associated costs. Costs and outcomes were discounted at a 3 % annual rate. Probabilistic sensitivity analysis was performed using 10,000 Monte Carlo simulations to assess the model robustness. Treatment and administration costs during the induction phase were higher for rituximab-bendamustine (€17,671) than for R-CHOP (€11,850). At the end of the 25-year period, the rituximab-bendamustine first-line strategy had a total cost of €68,357 compared with €69,528 for R-CHOP. Health benefits were higher for rituximab-bendamustine treatment (10.31 QALYs) than for R-CHOP treatment (9.82 QALYs). In the probabilistic analysis, rituximab-bendamustine was the dominant strategy over treatment with R-CHOP in 53.4 % of the simulations. First-line therapy with rituximab-bendamustine in FL patients was the dominant strategy over treatment with R-CHOP; it showed cost

Assessment of Physicochemical Properties of Rituximab Related to Its Immunomodulatory Activity

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Mariana P. Miranda-Hernández

2015-01-01

Full Text Available Rituximab is a chimeric monoclonal antibody employed for the treatment of CD20-positive B-cell non-Hodgkin’s lymphoma, chronic lymphocytic leukemia, rheumatoid arthritis, granulomatosis with polyangiitis and microscopic polyangiitis. It binds specifically to the CD20 antigen expressed on pre-B and consequently on mature B-lymphocytes of both normal and malignant cells, inhibiting their proliferation through apoptosis, CDC, and ADCC mechanisms. The immunomodulatory activity of rituximab is closely related to critical quality attributes that characterize its chemical composition and spatial configuration, which determine the recognition of CD20 and the binding to receptors or factors involved in its effector functions, while regulating the potential immunogenic response. Herein, we present a physicochemical and biological characterization followed by a pharmacodynamics and immunogenicity study to demonstrate comparability between two products containing rituximab. The physicochemical and biological characterization revealed that both products fit within the same response intervals exhibiting the same degree of variability. With regard to clinical response, both products depleted CD20+ B-cells until posttreatment recovery and no meaningful differences were found in their pharmacodynamic profiles. The evaluation of anti-chimeric antibodies did not show differential immunogenicity among products. Overall, these data confirm that similarity of critical quality attributes results in a comparable immunomodulatory activity.

Standardization of Procedures for the Preparation of (177)Lu- and (90)Y-labeled DOTA-Rituximab Based on the Freeze-dried Kit Formulation.

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Wojdowska, Wioletta; Karczmarczyk, Urszula; Maurin, Michal; Garnuszek, Piotr; Mikołajczak, Renata

2015-01-01

Rituximab when radiolabelled with (177)Lu or (90)Y has been investigated for the treatment of patients with Non-Hodgkin's Lymphoma. In this study, we optimized the preparation of antibody conjugates with chelating agent in the freeze-dried kit. It shortens procedures needed for the successful radiolabeling with lutetium-177 and yttrium-90 and assures reproducible labelling yields. Various molar ratios of Rituximab:DOTA (from 1:5 to 1:100) were used at the conjugation step and different purification method to remove unbound DOTA were investigated (size-exclusion chromatography, dialysis, ultrafiltration). The final monoclonal antibody concentration was quantified by Bradford method, and the number of DOTA molecules was determined by radiolabeling assay using (64)Cu. The specific activity of (177)Lu-DOTA-Rituximab and (90)Y-DOTA-Rituximab were optimized using various amounts of radiometal. Quality control (SE-HPLC, ITLC) and stability study were performed. An average of 4.2 ± 0.8 p-SCN-Bz-DOTA molecules could be randomly conjugated to a single molecule of Rituximab. The ultrafiltration system was the most efficient for purification and resulted in the highest recovery efficiency (77.2%). At optimized conditions the (177)Lu-DOTARituximab and (90)Y-DOTA-Rituximab were obtained with radiochemical purity >99% and specific activity ca. 600 MBq/mg. The radioimmunoconjugates were stable in human serum and 0.9% NaCl. After 72 h of incubation the radiochemical purity of (177)Lu-DOTA-Rituximab decreased to 94% but it was still more than 88% for (90)Y-DOTA-Rituximab. The radioimmunoconjugate showed stability after six months storage at 2 - 8(0)C, as a lyophilized formulation. Our study shows that Rituximab-DOTA can be efficiently radiolabeled with (177)Lu and (90)Y via p-SCN-Bn-DOTA using a freezedried kit.

Four cases of recalcitrant pemphigus vulgaris salvaged with rituximab

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Samyak Ganjre

2017-01-01

Full Text Available Although the long-term use of immunosuppressives – supplemented with more aggressive treatments such as immunoadsorption, intravenous immunoglobulins, or plasmapheresis in recalcitrant cases has dramatically improved the prognosis of pemphigus vulgaris, opportunistic infections secondary to immunosuppression continue to cause significant mortality. We report four cases– three old ones, who had accumulated significant morbidities over their disease duration ranging from 5 to 10 years, and the fourth, a teenage female intolerant to corticosteroids and idiosyncratic to methotrexate– who achieved complete remission on administration of rituximab by the lymphoma protocol. One of the old cases who had recalcitrant mucositis experienced its complete subsidence without any adjuvant whatsoever. All continue to remain asymptomatic for 11–20 months. None had infusion reactions or any delayed side effects.

Pre-emptive rituximab for Epstein-Barr virus reactivation after haplo-hematopoietic stem cell transplantation.

Science.gov (United States)

Kobayashi, Shogo; Sano, Hideki; Mochizuki, Kazuhiro; Ohara, Yoshihiro; Takahashi, Nobuhisa; Ohto, Hitoshi; Kikuta, Atsushi

2017-09-01

Epstein-Barr virus-related post-transplantation lymphoproliferative disease (EBV-PTLD) is a serious complication in hematopoietic stem cell transplantation (HSCT) recipients. We conducted a retrospective study to investigate the incidence and potential risk factors for EBV reactivation and to assess the efficacy of the management of EBV reactivation with pre-emptive rituximab in children who had T-cell-replete haploidentical HSCT (TCR-haplo-SCT) with low-dose anti-thymocyte globulin (ATG). EBV-DNA level in peripheral blood (PB) was measured when suspected EBV reactivation were observed. When the EBV-DNA level in PB increased to >1,000 copies/10 6 peripheral blood mononuclear cells (PBMC), patients were pre-emptively treated with rituximab (375 mg/m 2 /dose). A total of 19 (50%) of 38 patients received rituximab infusion at a median time of 56 days after HSCT (range, 17-270 days). The median viral load at initiation of therapy was 2,900 copies/10 6 PBMC (range, 1,000-650 000). Pre-emptive therapy was started after a median of 2 days (range, 0-7 days). The median number of weekly treatment cycles was 2 (range, 1-3). None of the patients developed PTLD or other EBV-associated diseases. Pre-emptive rituximab therapy could be a useful strategy for EBV-PTLD in TCR-haplo-SCT recipients with low-dose ATG. © 2017 Japan Pediatric Society.

Microcosting Study of Rituximab Subcutaneous Injection Versus Intravenous Infusion

NARCIS (Netherlands)

Mihajloviç, Jovan; Bax, Pieter; van Breugel, Erwin; Blommestein, Hedwig M.; Hoogendoorn, Mels; Hospes, Wobbe; Postma, Maarten J.

Purpose: The goal of this study is to identify and compare all direct costs of intravenous and subcutaneous rituximab given to patients with diffuse large B-cell lymphoma in the Netherlands.  Methods: Using a prospective, observational, bottom-up microcosting study, we collected primary data on the

Chemokine/cytokine profiling after rituximab: reciprocal expression of BCA-1/CXCL13 and BAFF in childhood OMS.

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Pranzatelli, Michael R; Tate, Elizabeth D; Travelstead, Anna L; Verhulst, Steven J

2011-03-01

The aim of the study was to test the hypothesis that B-cell repopulation following rituximab (anti-CD20) therapy is orchestrated by chemokines and non-chemokine cytokines. Twenty-five children with opsoclonus-myoclonus syndrome (OMS) received rituximab with or without conventional agents. A comprehensive panel of 40 chemokines and other cytokines were measured in serum by ELISA and multiplexed fluorescent bead-based immunoassay. Serum BAFF concentration changed dramatically (even after first infusion) and inversely with B-cell depletion/repopulation and CXCL13 concentration at 1, 3, and 6 months. Negative correlations were found for BAFF concentration vs blood B cell percentage and serum CXCL13 concentration; positive correlations with serum rituximab concentrations. Six months after initiation of therapy, no significant difference in the levels of APRIL, CXCL10, IL-6, or 17 other cytokines/chemokines were detected. These data reveal a major role for BAFF in peripheral B cell repopulation following rituximab-induced B-cell depletion, and novel changes in CXCL13. ClinicalTrials.gov NCT0024436. Copyright © 2010 Elsevier Ltd. All rights reserved.

Immunological profile in cerebrospinal fluid of patients with multiple sclerosis after treatment switch to rituximab and compared with healthy controls.

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Pierre de Flon

Full Text Available To investigate changes in the cerebrospinal fluid (CSF immunological profile after treatment switch from first-line injectables to rituximab in patients with relapsing-remitting MS (RRMS, and to compare the profile in MS patients with healthy controls (HC.Cerebrospinal fluid from 70 patients with clinically stable RRMS and 55 HC was analysed by a multiplex electrochemiluminescence method for a broad panel of cytokines and immunoactive substances before, and over a two-year period after, treatment switch to rituximab. After quality assessment of data, using a predefined algorithm, 14 analytes were included in the final analysis.Ten of the 14 analytes differed significantly in MS patients compared with HC at baseline. Levels of IP-10 (CXCL10, IL-12/23p40, IL-6, sVCAM1, IL-15, sICAM1 and IL-8 (CXCL8 decreased significantly after treatment switch to rituximab. The cytokines IP-10 and IL-12/IL-23p40 displayed the largest difference versus HC at baseline and also the largest relative reduction after therapy switch to rituximab.We found significant changes in the immunological profile after therapy switch to rituximab in RRMS in the direction towards the values of HC. IP-10 and IL12/IL-23p40 deserve further studies as part of the immunopathogenesis of MS as well as for the mode of action of rituximab in MS.

Long-Term Maintenance Therapy Using Rituximab-Induced Continuous B-Cell Depletion in Patients with ANCA Vasculitis

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Pendergraft, William F.; Cortazar, Frank B.; Wenger, Julia; Murphy, Andrew P.; Rhee, Eugene P.; Laliberte, Karen A.; Niles, John L.

2014-01-01

Background and objectives Remission in the majority of ANCA vasculitis patients is not sustained after a single course of rituximab, and risk of relapse warrants development of a successful strategy to ensure durable remission. Design, setting, participants, & measurements A retrospective analysis of ANCA vasculitis patients who underwent maintenance therapy using rituximab-induced continuous B-cell depletion for up to 7 years was performed. Maintenance therapy with rituximab was initiated after achieving remission or converting from other prior maintenance therapy. Continuous B-cell depletion was achieved in all patients by scheduled rituximab administration every 4 months. Disease activity, serologic parameters, adverse events, and survival were examined. Results In the study, 172 patients (mean age=60 years, 55% women, 57% myeloperoxidase–ANCA) treated from April of 2006 to March of 2013 underwent continuous B-cell depletion with rituximab. Median remission maintenance follow-up time was 2.1 years. Complete remission (Birmingham Vasculitis Activity Score [BVAS]=0) was achieved in all patients. Major relapse (BVAS≥3) occurred in 5% of patients and was associated with weaning of other immunosuppression drugs. Remission was reinduced in all patients. Survival mirrored survival of a general age-, sex-, and ethnicity-matched United States population. Conclusion This analysis provides evidence for long-term disease control using continuous B-cell depletion. This treatment strategy in ANCA vasculitis patients also seems to result in survival rates comparable with rates in a matched reference population. These findings suggest that prospective remission maintenance treatment trials using continuous B-cell depletion are warranted. PMID:24626432

Rituximab (MabThera) til behandling af aktiv reumatoid artritis

DEFF Research Database (Denmark)

El Fassi, Daniel; Nielsen, Claus Henrik; Bendtzen, Klaus

2006-01-01

Rituximab (RTX) is a murine/human monoclonal antibody to CD20, a protein expressed almost exclusively on human B-lymphocytes. RTX induces rapid and marked B-cell depletion with beneficial clinical effects in 1/3 to 1/2 of rheumatoid arthritis patients. Treatment is given as two iv. infusions with...

Dosimetric analysis of 177Lu-DOTA-rituximab in patients with relapsed/refractory non-Hodgkin's lymphoma.

Science.gov (United States)

Yadav, Madhav P; Singla, Suhas; Thakral, Parul; Ballal, Sanjana; Bal, Chandrasekhar

2016-07-01

Radioimmunotherapy targeting CD20 receptors in lymphoma using radiolabeled chimeric antibodies may lead to better therapeutic responses than cold anti-CD20 antibodies. This study aimed to assess the biodistribution and present reasonable estimates of normal organ doses, including red marrow using Lu-DOTA-rituximab. Patients with relapsed/refractory CD20+ B-cell non-Hodgkin's lymphoma were recruited into this prospective study. In-house labeling of Lu-DOTA-rituximab was performed and administered after quality assurance. Rituximab (375 mg/m), followed by 50 mCi (1850 MBq) of Lu-DOTA-rituximab was administered as a slow intravenous infusion and emission images were acquired. Regions of interest were drawn for kidney, liver, heart, bladder, spleen, and tumor lesions on both anterior and posterior images. Internal dose estimation was performed using OLINDA v1.0 software. The mean age of the 10 patients (eight men and two women) was 52±13 years. The uptake of radiolabeled antibody was visualized within 30 min of administration in the liver, kidneys, heart, spleen, and bladder. The coefficient of determination (R) was greater than 0.95 for organs and the whole body in all patients. The effective half-life of radioimmunoconjugate was 100±28 h (42-126 h). The critical organ in our study was the red marrow. The average total body dose, effective dose, and effective dose equivalent calculated in all 10 patients were 0.13±0.02, 0.15±0.03, and 0.22±0.04 mGy/MBq, respectively. There may be considerable interindividual differences in absorbed doses of organs and generalization or extrapolation of doses in the clinical setting at present is not feasible with Lu-DOTA-rituximab in non-Hodgkin's lymphoma patients. Patient-specific dosimetry is thus recommended to eliminate the variations and reduce the possibility of dose-limiting toxicity.

RadCon Occurrence Reporting Simplified

International Nuclear Information System (INIS)

Denham, D. H.

1999-01-01

This narrative and accompanying diagrams provide a simplified summary of the RadCon Occurrence Reporting criteria to allow Environmental Restoration Contractor (ERC) staff to efficiently recognize occurrences and to effectively initiate the implementation of the requirements of U.S. Department of Energy (DOE) Order 232.1A, Occurrence Reporting and Processing of Operations Information, and of the ERC criteria defined in BHI-MA-02, ERC Project Procedures, Procedure 2.6, ''Occurrence Investigation and Reporting.'' These directives promote timely identification, categorization, notification, and reporting to DOE and ERC management of reportable occurrences at DOE-owned or -operated facilities that could (1) affect health and safety of the public, (2) seriously impact the intended purpose of DOE facilities, (3) adversely affect the credibility of DOE, or (4) have a noticeable adverse effect on the environment

Bendamustine and rituximab (BR) versus dexamethasone, rituximab, and cyclophosphamide (DRC) in patients with Waldenström macroglobulinemia.

Science.gov (United States)

Paludo, Jonas; Abeykoon, Jithma P; Shreders, Amanda; Ansell, Stephen M; Kumar, Shaji; Ailawadhi, Sikander; King, Rebecca L; Koehler, Amber B; Reeder, Craig B; Buadi, Francis K; Dispenzieri, Angela; Lacy, Martha Q; Dingli, David; Witzig, Thomas E; Go, Ronald S; Gonsalves, Wilson I; Kourelis, Taxiarchis; Warsame, Rahma; Leung, Nelson; Habermann, Thomas M; Hayman, Suzanne; Lin, Yi; Kyle, Robert A; Rajkumar, S Vincent; Gertz, Morie A; Kapoor, Prashant

2018-04-03

The treatment approaches for Waldenstrom macroglobulinemia (WM) are largely based upon information from single-arm phase II trials, without comparative data. We compared the efficacy of two commonly used regimens in routine practice (bendamustine-rituximab (BR) and dexamethasone, rituximab plus cyclophosphamide (DRC)) and evaluated their activity with respect to the patients' MYD88 L265P mutation status. Of 160 consecutive patients, 60 received BR (43 with relapsed/refractory WM) and 100 received DRC (50 had relapsed/refractory WM). In the treatment-naïve setting, overall response rate (ORR) was 93% with BR versus 96% with DRC (p = 0.55). Two-year progression-free survival (PFS) with BR and DRC was 88 and 61%, respectively (p = 0.07). In salvage setting, ORR was 95% with BR versus 87% with DRC, p = 0.45; median PFS with BR was 58 versus 32 months with DRC (2-year PFS was 66 versus 53%; p = 0.08). Median disease-specific survival was not reached with BR versus 166 months with DRC (p = 0.51). The time-to-event endpoints and depth of response were independent of the MYD88 mutation status. Grade ≥ 3 adverse events of both regimens were comparable. A trend for longer PFS was observed with BR although the regimens have comparable toxicities. The activity of BR and DRC appears to be unaffected by patients' MYD88 mutation status.

Efficacy and Safety of Prolonged Rituximab Treatment in Patients with Systemic Juvenile Idiopathic Arthritis

Directory of Open Access Journals (Sweden)

E. I. Alexeeva

2013-01-01

Full Text Available Aim: to assess efficacy and safety of rituximab treatment in children with systemic juvenile idiopathic arthritis under prolonged follow-up. Patients and methods: results of treatment of 60 children (33 girls and 27 boys with systemic variant of juvenile idiopathic arthritis being followed-up in rheumatology department of the Federal State Institution «Scientific Centre of Children Health» of RAMS (FSI «SCCH» RAMS were analyzed. The mean age of children was 8,7 years. The mean duration of disease course at the moment of first rituximab administration was 5,3 years. At the beginning of rituximab therapy all children had active articular syndrome, severe systemic manifestations and significantly increased laboratory markers of activity. As the signs of improvement the authors used pediatric criteria of the American College of Rheumatology. The treatment was approved by the local ethic committee of the FSI «SCCH» RAMS; the patients’ representatives and patients older than 14 years old had signed informed agreement. Results: remission was induced in 26 of 60 (43% patients: in 9 of them after the 1st course of treatment, in 8 — after the 2nd, in 6 — after the 3d and in 3 — after the 4th. The maximal duration of remission was 5 years 4 months, minimal — 6 months. Other genetically engineered drugs were administered to 34 (57% of the patients: due to the primary inefficiency in 15, secondary inefficiency — in 10; due to partial inefficiency — in 9 children. The drug was well-tolerated in most of the patients. Undesirable effects were represented by transfusional reactions to the rituximab infusion, infections with different severity and granulocytopenia. Conclusions: rituximab has high efficiency in patients with severe systemic variant of juvenile idiopathic arthritis. The drug induced remission in patients who had been considered almost incurable, with low status of physical and social adaptation.

Reduction of fatigue in Sjögren syndrome with rituximab: results of a randomised, double-blind, placebo-controlled pilot study.

Science.gov (United States)

Dass, S; Bowman, S J; Vital, E M; Ikeda, K; Pease, C T; Hamburger, J; Richards, A; Rauz, S; Emery, P

2008-11-01

Primary Sjögren syndrome (pSS) causes significant systemic symptoms including fatigue as well as glandular dysfunction. There are currently no effective systemic therapies; however, open label series have suggested that rituximab may be beneficial for systemic and glandular manifestations. Therefore, we performed a double blind, placebo-controlled, randomised pilot study of the efficacy of rituximab in reducing fatigue in pSS. A total of 17 patients with pSS and a score on fatigue visual analogue scale (VAS) >50 were randomised to receive either 2 infusions of rituximab 1 g or placebo; patients also received oral and intravenous steroids. Outcome measures included: the proportion of patients with >20% reduction in fatigue VAS, changes in pSS related symptoms, health related quality of life and immunological parameters of pSS. These were measured 6 months after therapy. There was significant improvement from baseline in fatigue VAS in the rituximab group (p<0.001) in contrast to the placebo group (p = 0.147). There was a significant difference between the groups at 6 months in the social functioning score of SF-36 (p = 0.01) and a trend to significant difference in the mental health domain score of SF-36 (p = 0.06). There was one episode of serum sickness in the rituximab treated group. This is the first double blind study of rituximab in pSS to show benefit; further studies are justified.

Feasibility and toxicity of concomitant radio/immunotherapy with MabThera (Rituximab {sup registered}) for patients with non-Hodgkin's lymphoma. Results of a prospective phase I/II study

Energy Technology Data Exchange (ETDEWEB)

Haidenberger, Alfred; Popper, Bela-Andre; Skvortsova, Ira; Lukas, Peter [Medical Univ. Innsbruck (Austria). Dept. of Radiotherapy/Radiooncology; Fromm-Haidenberger, Sabine [Hospital Gmunden (Austria). Inst. of Radiology; Vries, Alexander de [Hospital Feldkirch (Austria). Dept. of Radiotherapy/Radiooncology; Steurer, Michael; Kantner, Johanna; Gunsilius, Eberhard [Medical Univ. Innsbruck (Austria). Dept. of Hematology

2011-05-15

Purpose: Non-Hodgkin's lymphomas (NHL) have a high radio- and chemosensitivity. Although initially responsive, approximately 50% of low grade B-cell lymphomas relapse after 10-15 years. Besides chemo- and radiotherapy, rituximab, a mouse/human chimeric antibody targeting CD20 antigen on the surface of B-cell lymphoma cells, is another treatment approach. In vitro data showed potentiation of radiation-induced apoptosis by addition of rituximab. The purpose of this study was to evaluate the feasibility and toxicity of radiotherapy with concomitant application of rituximab in NHL patients. Patients and Methods: A total of 21 patients with B-cell lymphoma (stage I: n = 11; II: n = 5; III: n = 1; IV: n = 4) were included in this study, treated with radiotherapy of 30-40 Gy and weekly application of rituximab (375 mg/m{sup 2}). Nine patients had R-CHOP chemotherapy previously, 1 patient leuceran chemotherapy, and 2 patients an initial treatment with 6 cycles of rituximab. Mean time of follow-up was 41.7 months. Results: No grade 4 toxicity or treatment-related death was observed. In 1 patient, rituximab application had to be stopped after 3 cycles due to radiation-induced side effects. No late toxicities were reported. All patients were in complete remission after treatment. Progression or relapse was observed in 6 patients (28%); the mean time to progression was 27 months. The mean overall survival (OS) was 53 months. Conclusion: Combined radio/immunotherapy is feasible and safe. Treatment was well tolerated, no late toxicities were observed, and treatment outcome is promising. Randomized trials are necessary to clarify the benefit of this treatment approach and its applicability. (orig.)

EFFICACY OF RECURRENT RITUXIMAB TREATMENT IN PATIENT WITH SEVERE REFRACTORY SYSTEMIC JUVENILE RHEUMATOID ARTHRITIS

Directory of Open Access Journals (Sweden)

E.I. Alexeeva

2011-01-01

Full Text Available The article contains clinical case description of a severe systemic juvenile rheumatoid arthritis, that was refractory to classic immunosuppressant therapy. The disease was characterized by such extraarticular manifestations as fever, lymphadenopathy,  hepatosplenomegaly, polyserositis, generalized joint involvement and high activity in lab tests. As a result of severe clinical course of the disease, patients develop bilateral aseptic bone necrosis in coxofemoral joints and coxarthrosis. Against the background of glucocorticosteroid treatment the patient has developed hormone-dependency and hormone resistance. Inclusion into the treatment of anti-CD20 monoclonal antibodies (rituximab has stopped systemic manifestations of the disease, inflammation in the joints, normalized lab activity rates. The positive therapeutic effect allowed to perform surgery due to bilateral coxarthrosis. These results show that rituximab is highly effective in children with systemic juvenile rheumatoid arthritis, that is resistant to classic immunosupressants and glucocorticoides. Key words: children, systemic juvenile rheumatoid arthritis, rituximab, recurrent treatment, prosthetics, hip joint. (Voprosy sovremennoi pediatrii — Current Pediatrics. — 2011; 10 (5: 157–163.

Ibrutinib for patients with rituximab-refractory Waldenström's macroglobulinaemia (iNNOVATE): an open-label substudy of an international, multicentre, phase 3 trial.

Science.gov (United States)

Dimopoulos, Meletios A; Trotman, Judith; Tedeschi, Alessandra; Matous, Jeffrey V; Macdonald, David; Tam, Constantine; Tournilhac, Olivier; Ma, Shuo; Oriol, Albert; Heffner, Leonard T; Shustik, Chaim; García-Sanz, Ramón; Cornell, Robert F; de Larrea, Carlos Fernández; Castillo, Jorge J; Granell, Miquel; Kyrtsonis, Marie-Christine; Leblond, Veronique; Symeonidis, Argiris; Kastritis, Efstathios; Singh, Priyanka; Li, Jianling; Graef, Thorsten; Bilotti, Elizabeth; Treon, Steven; Buske, Christian

2017-02-01

In the era of widespread rituximab use for Waldenström's macroglobulinaemia, new treatment options for patients with rituximab-refractory disease are an important clinical need. Ibrutinib has induced durable responses in previously treated patients with Waldenström's macroglobulinaemia. We assessed the efficacy and safety of ibrutinib in a population with rituximab-refractory disease. This multicentre, open-label substudy was done at 19 sites in seven countries in adults aged 18 years and older with confirmed Waldenström's macroglobulinaemia, refractory to rituximab and requiring treatment. Disease refractory to the last rituximab-containing therapy was defined as either relapse less than 12 months since last dose of rituximab or failure to achieve at least a minor response. Key exclusion criteria included: CNS involvement, a stroke or intracranial haemorrhage less than 12 months before enrolment, clinically significant cardiovascular disease, hepatitis B or hepatitis C viral infection, and a known bleeding disorder. Patients received oral ibrutinib 420 mg once daily until progression or unacceptable toxicity. The substudy was not prospectively powered for statistical comparisons, and as such, all the analyses are descriptive in nature. This study objectives were the proportion of patients with an overall response, progression-free survival, overall survival, haematological improvement measured by haemoglobin, time to next treatment, and patient-reported outcomes according to the Functional Assessment of Cancer Therapy-Anemia (FACT-An) and the Euro Qol 5 Dimension Questionnaire (EQ-5D-5L). All analyses were per protocol. The study is registered at ClinicalTrials.gov, number NCT02165397, and follow-up is ongoing but enrolment is complete. Between Aug 18, 2014, and Feb 18, 2015, 31 patients were enrolled. Median age was 67 years (IQR 58-74); 13 (42%) of 31 patients had high-risk disease per the International Prognostic Scoring System Waldenstr

IMPACT OF PRE-TRANSPLANT RITUXIMAB ON SURVIVAL AFTER AUTOLOGOUS HEMATOPOIETIC STEM CELL TRANSPLANTATION FOR DIFFUSE LARGE B-CELL LYMPHOMA

Science.gov (United States)

Fenske, Timothy S.; Hari, Parameswaran N.; Carreras, Jeanette; Zhang, Mei-Jie; Kamble, Rammurti T.; Bolwell, Brian J.; Cairo, Mitchell S.; Champlin, Richard E.; Chen, Yi-Bin; Freytes, César O.; Gale, Robert Peter; Hale, Gregory A.; Ilhan, Osman; Khoury, H. Jean; Lister, John; Maharaj, Dipnarine; Marks, David I.; Munker, Reinhold; Pecora, Andrew L.; Rowlings, Philip A.; Shea, Thomas C.; Stiff, Patrick; Wiernik, Peter H.; Winter, Jane N.; Rizzo, J. Douglas; van Besien, Koen; Lazarus, Hillard M.; Vose, Julie M.

2010-01-01

Incorporation of the anti-CD20 monoclonal antibody rituximab into front-line regimens for diffuse large B-cell lymphoma (DLBCL) has resulted in improved survival. Despite this progress, many patients develop refractory or recurrent DLBCL and then receive autologous hematopoietic stem cell transplantation (AuHCT). It is unclear to what extent pre-transplant exposure to rituximab affects outcomes following AuHCT. Outcomes of 994 patients receiving AuHCT for DLBCL between 1996 and 2003 were analyzed according to whether rituximab was (n=176, “+R” group) or was not (n=818, “ −R” group) administered with front-line or salvage therapy prior to AuHCT. The +R group had superior progression-free survival (50% versus 38%, p=0.008) and overall survival (57% versus 45%, p=0.006) at 3 years. Platelet and neutrophil engraftment were not affected by exposure to rituximab. Non-relapse mortality (NRM) did not differ significantly between the +R and −R groups. In multivariate analysis, the +R group had improved progression-free survival (relative risk of relapse/progression or death 0.64, p<0.001) and improved overall survival (relative risk of death of 0.74, p=0.039). We conclude that pre-transplant rituximab is associated with a lower rate of progression and improved survival following AuHCT for DLBCL, with no evidence of impaired engraftment or increased NRM. PMID:19822306

A multi-centre retrospective study of rituximab use in the treatment of relapsed or resistant warm autoimmune haemolytic anaemia.

LENUS (Irish Health Repository)

Maung, Su W

2013-10-01

This retrospective analysis assessed the response, safety and duration of response to standard dose rituximab 375 mg\\/m(2) weekly for four weeks as therapy for patients with primary or secondary warm autoimmune haemolytic anaemia (WAIHA), who had failed initial treatment. Thirty-four patients received rituximab for WAIHA in seven centres in the Republic of Ireland. The overall response rate was 70·6% (24\\/34) with 26·5% (9\\/34) achieving a complete response (CR). The time to response was 1 month post-initiation of rituximab in 87·5% (21\\/24) and 3 months in 12·5% (3\\/24) of patients. The median duration of follow-up was 36 months (range 6-90 months). Of the patients who responded, 50% (12\\/24) relapsed during follow up with a median time to next treatment of 16·5 months (range 6-60 months). Three patients were re-treated with rituximab 375 mg\\/m2 weekly for four weeks at relapse and responded. There was a single episode of neutropenic sepsis. Rituximab is an effective and safe treatment for WAIHA but a significant number of patients will relapse in the first two years post treatment. Re-treatment was effective in a small number of patients, suggesting that intermittent pulse treatment or maintenance treatment may improve long-term response.

Púrpura trombocitopênica trombótica - remissão completa em paciente com mau prognóstico após tratamento com plasmaférese terapêutica e rituximabe Successful outcome in poor-prognostic acute thrombotic thrombocytopenic purpura treated with plasma exchange and rituximab

Directory of Open Access Journals (Sweden)

Cesar de Almeida Neto

2008-02-01

Full Text Available A púrpura trombocitopênica trombótica (PTT é uma doença rara e fatal que deve ser diagnosticada e tratada prontamente a fim de se obter melhor resposta terapêutica. Apresentamos um caso de PTT aguda grave tratada com plasmaférese e rituximabe. Ao diagnóstico, a paciente apresentava anemia hemolítica microangiopática, icterícia, febre, convulsões, seguidas por coma e choque hipovolêmico. Os exames laboratoriais iniciais mostravam DHL=2.860 IU/L, contagem de plaquetas de 37 x 10(9/L, hemoglobina de 5,1 g/dL e no esfregaço de sangue periférico havia a presença de esquizócitos. Iniciado tratamento para PTT com pulsoterapia com metilprednisolona e plasmaféreses terapêuticas diárias com troca de uma volemia plasmática e substituição com plasma fresco congelado. Após cinco sessões de plasmaférese, houve piora no quadro neurológico, acompanhado por aumento importante de DHL, ALT, AST e a contagem de plaquetas era de 72 x 10(9/L. Iniciamos o uso de rituximabe na dose padrão de 375mg/m²/semana/4 semanas e passamos a utilizar plasma pobre em crioprecipitado como reposição durante as plasmaféreses. Dois dias após a mudança na conduta terapêutica, houve importante melhora do quadro neurológico, estabilização da contagem de plaquetas e queda acentuada de DHL. Após 23 procedimentos de plasmaférese e quatro doses de rituximabe, a paciente apresentou remissão completa, mantida há 34 meses. A plasmaférese terapêutica com plasma pobre em crioprecipitado e o uso concomitante de rituximabe foi uma estratégia útil no tratamento deste caso de PTT aguda grave. Porém, ensaios clínicos prospectivos e randomizados são necessários para confirmar estes achados.Thrombotic thrombocytopenic purpura (TTP is a rare severe disease that must be diagnosed and treated promptly for a successful outcome. We report a case of severe acute TTP treated with plasma exchange and rituximab. The patient presented at diagnosis with severe

Autoantibody levels in myositis patients correlate with clinical response during B cell depletion with rituximab.

Science.gov (United States)

Aggarwal, Rohit; Oddis, Chester V; Goudeau, Danielle; Koontz, Diane; Qi, Zengbiao; Reed, Ann M; Ascherman, Dana P; Levesque, Marc C

2016-06-01

To determine the longitudinal trends in serum levels of four myositis-associated autoantibodies: anti-Jo-1, -transcription intermediary factor 1 γ (TIF1-γ), -signal recognition particle (SRP) and -Mi-2, after B cell depletion with rituximab, and to determine the longitudinal association of these autoantibody levels with disease activity as measured by myositis core-set measures (CSMs). Treatment-resistant adult and pediatric myositis subjects (n = 200) received rituximab in the 44-week Rituximab in Myositis Trial. CSMs [muscle enzymes, manual muscle testing (MMT), physician and patient global disease activity, HAQ, and extramuscular disease activity] were evaluated monthly and anti-Jo-1 (n = 28), -TIF1-γ (n = 23), -SRP (n = 25) and -Mi-2 (n = 26) serum levels were measured using validated quantitative ELISAs. Temporal trends and the longitudinal relationship between myositis-associated autoantibodies levels and CSM were estimated using linear mixed models. Following rituximab, anti-Jo-1 levels decreased over time (P myositis subjects decreased after B cell depletion and were correlated with changes in disease activity, whereas anti-SRP levels were only associated with longitudinal muscle enzyme levels. The strong association of anti-Jo-1 levels with clinical outcomes suggests that anti-Jo-1 autoantibodies may be a good biomarker for disease activity. © The Author 2016. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Lenalidomide-bendamustine-rituximab in untreated mantle cell lymphoma > 65 years with untreated mantle cell lymphoma

DEFF Research Database (Denmark)

Albertsson-Lindblad, Alexandra; Kolstad, Arne; Laurell, Anna

2016-01-01

For elderly patients with mantle cell lymphoma (MCL), there is no defined standard therapy. In this multicenter open-label phase I/II trial we evaluated the addition of lenalidomide (LEN) to rituximab-bendamustine (R-B) as first-line treatment to elderly MCL patients. Patients >65 years with untr......For elderly patients with mantle cell lymphoma (MCL), there is no defined standard therapy. In this multicenter open-label phase I/II trial we evaluated the addition of lenalidomide (LEN) to rituximab-bendamustine (R-B) as first-line treatment to elderly MCL patients. Patients >65 years...

Novel assessment tools to evaluate clinical and laboratory responses in a subset of patients enrolled in the Rituximab in Myositis trial.

Science.gov (United States)

Rider, Lisa G; Yip, Adrienne L; Horkayne-Szakaly, Iren; Volochayev, Rita; Shrader, Joseph A; Turner, Maria L; Kong, Heidi H; Jain, Minal S; Jansen, Anna V; Oddis, Chester V; Fleisher, Thomas A; Miller, Frederick W

2014-01-01

We aimed to assess changes in myositis core set measures and ancillary clinical and laboratory data from the National Institutes of Health's subset of patients enrolled in the Rituximab in Myositis trial. Eighteen patients (5 dermatomyositis, 8 polymyositis, 5 juvenile dermatomyositis) completed more in-depth testing of muscle strength and cutaneous assessments, patient-reported outcomes, and laboratory tests before and after administration of rituximab. Percentage change in individual measures and in the definitions of improvement (DOIs) and standardized response means were examined over 44 weeks. Core set activity measures improved by 18-70% from weeks 0-44 and were sensitive to change. Fifteen patients met the DOI at week 44, 9 patients met a DOI 50% response, and 4 met a DOI 70% response. Muscle strength and function measures were more sensitive to change than cutaneous assessments. Constitutional, gastrointestinal, and pulmonary systems improved 44-70%. Patient-reported outcomes improved up to 28%. CD20+ B cells were depleted in the periphery, but B cell depletion was not associated with clinical improvement at week 16. This subset of patients had high rates of clinical response to rituximab, similar to patients in the overall trial. Most measures were responsive, and muscle strength had a greater degree of change than cutaneous assessments. Several novel assessment tools, including measures of strength and function, extra-muscular organ activity, fatigue, and health-related quality of life, are promising for use in future myositis trials. Further study of B cell-depleting therapies in myositis, particularly in treatment-naïve patients, is warranted.

Rituximab Extended Schedule or Re-Treatment Trial for Low–Tumor Burden Follicular Lymphoma: Eastern Cooperative Oncology Group Protocol E4402

Science.gov (United States)

Kahl, Brad S.; Hong, Fangxin; Williams, Michael E.; Gascoyne, Randy D.; Wagner, Lynne I.; Krauss, John C.; Habermann, Thomas M.; Swinnen, Lode J.; Schuster, Stephen J.; Peterson, Christopher G.; Sborov, Mark D.; Martin, S. Eric; Weiss, Matthias; Ehmann, W. Christopher; Horning, Sandra J.

2014-01-01

Purpose In low–tumor burden follicular lymphoma (FL), maintenance rituximab (MR) has been shown to improve progression-free survival when compared with observation. It is not known whether MR provides superior long-term disease control compared with re-treatment rituximab (RR) administered on an as-needed basis. E4402 (RESORT) was a randomized clinical trial designed to compare MR against RR. Patients and Methods Eligible patients with previously untreated low–tumor burden FL received four doses of rituximab, and responding patients were randomly assigned to either RR or MR. Patients receiving RR were eligible for re-treatment at each disease progression until treatment failure. Patients assigned to MR received a single dose of rituximab every 3 months until treatment failure. The primary end point was time to treatment failure. Secondary end points included time to first cytotoxic therapy, toxicity, and health-related quality of life (HRQOL). Results A total of 289 patients were randomly assigned to RR or MR. With a median follow-up of 4.5 years, the estimated median time to treatment failure was 3.9 years for patients receiving RR and 4.3 years for those receiving MR (P = .54). Three-year freedom from cytotoxic therapy was 84% for those receiving RR and 95% for those receiving MR (P = .03). The median number of rituximab doses was four patients receiving RR and 18 for those receiving MR. There was no difference in HRQOL. Grade 3 to 4 toxicities were infrequent in both arms. Conclusion In low–tumor burden FL, a re-treatment strategy uses less rituximab while providing disease control comparable to that achieved with a maintenance strategy. PMID:25154829

Identification of Fc Gamma Receptor Glycoforms That Produce Differential Binding Kinetics for Rituximab.

Science.gov (United States)

Hayes, Jerrard M; Frostell, Asa; Karlsson, Robert; Müller, Steffen; Martín, Silvia Míllan; Pauers, Martin; Reuss, Franziska; Cosgrave, Eoin F; Anneren, Cecilia; Davey, Gavin P; Rudd, Pauline M

2017-10-01

Fc gamma receptors (FcγR) bind the Fc region of antibodies and therefore play a prominent role in antibody-dependent cell-based immune responses such as ADCC, CDC and ADCP. The immune effector cell activity is directly linked to a productive molecular engagement of FcγRs where both the protein and glycan moiety of antibody and receptor can affect the interaction and in the present study we focus on the role of the FcγR glycans in this interaction. We provide a complete description of the glycan composition of Chinese hamster ovary (CHO) expressed human Fcγ receptors RI (CD64), RIIa Arg131/His131 (CD32a), RIIb (CD32b) and RIIIa Phe158/Val158 (CD16a) and analyze the role of the glycans in the binding mechanism with IgG. The interactions of the monoclonal antibody rituximab with each FcγR were characterized and we discuss the CHO-FcγRIIIa Phe158/Val158 and CHO-FcγRI interactions and compare them to the equivalent interactions with human (HEK293) and murine (NS0) produced receptors. Our results reveal clear differences in the binding profiles of rituximab, which we attribute in each case to the differences in host cell-dependent FcγR glycosylation. The glycan profiles of CHO expressed FcγRI and FcγRIIIa Phe158/Val158 were compared with the glycan profiles of the receptors expressed in NS0 and HEK293 cells and we show that the glycan type and abundance differs significantly between the receptors and that these glycan differences lead to the observed differences in the respective FcγR binding patterns with rituximab. Oligomannose structures are prevalent on FcγRI from each source and likely contribute to the high affinity rituximab interaction through a stabilization effect. On FcγRI and FcγRIIIa large and sialylated glycans have a negative impact on rituximab binding, likely through destabilization of the interaction. In conclusion, the data show that the IgG1-FcγR binding kinetics differ depending on the glycosylation of the FcγR and further support a

Rapid infusion with rituximab: short term safety in systemic autoimmune diseases

DEFF Research Database (Denmark)

Larsen, Janni Lisander; Jacobsen, Soren

2013-01-01

To describe the incidence, types and severity of adverse events, related to an accelerated regime of rituximab infusion in patients with various autoimmune diseases. Fifty-four patients with systemic autoimmune disease, to be treated with 1,000 mg of rituximab twice 2 weeks apart, participated. Pre......-medication (oral prednisolone, anti-histamine and paracetamol) was administered 1-4 h before infusion start. The first infusion was administered over a period of 195 min. The second infusion over a period of 90 min. Any adverse events were classified using the Clinical Trials Classification of Adverse Events...... (CTCAE) v. 3.0. Ten patients (18.5%) experienced at least one infusion-related reaction (IRR) ever. The first infusion was associated with reactions in 4 CTCAE categories of which rhinitis were the most frequent. The CTCAE severity grading showed six patients (11.1%) had a grade 1 reaction. One patient...

Linfoma primario de hueso con afectación multicéntrica

Directory of Open Access Journals (Sweden)

Marcelo Graziadio

2012-10-01

Full Text Available El linfoma primario de hueso es una enfermedad infrecuente, que tiene una presentación y evolución diferente a los linfomas de otras localizaciones. Se presenta un caso de linfoma primario de hueso de localización craneana y esternal de rápido crecimiento. En su evolución, realizada la exéresis de la lesión primaria de calota, presentó aparición de nuevas lesiones de rápido crecimiento a nivel craneano y fémur y progresión de lesión preesternal que, con anatomía patológica de linfoma no Hodgkin difuso de células grandes B, inició R-CHOPP (ciclofosfamida, doxorrubicina, vincristina, prednisona y rituximab con rápida disminución de todas las lesiones sin evidencia de progresión al cabo de los seis ciclos.

Efficacy, outcomes, and cost-effectiveness of desensitization using IVIG and rituximab.

Science.gov (United States)

Vo, Ashley A; Petrozzino, Jeffrey; Yeung, Kai; Sinha, Aditi; Kahwaji, Joseph; Peng, Alice; Villicana, Rafael; Mackowiak, John; Jordan, Stanley C

2013-03-27

Transplantation rates are very low for the broadly sensitized patient (panel reactive antibody [PRA]>80%; HS). Here, we examine the efficacy, outcomes, and cost-effectiveness of desensitization using high-dose intravenous immunoglobulin (IVIG) and rituximab to improve transplantation rates in HS patients. From July 2006 to December 2011, 207 HS (56 living donors/151 deceased donors) patients (donor-specific antibody positive, PRA>80%) were desensitized using IVIG and rituximab. After desensitization, responsive patients proceeded to transplantation with an acceptable crossmatch. Cost and outcomes of desensitization were compared with dialysis. Of the 207 treated patients, 146 (71%) were transplanted. At 48 months, patient and graft survival by Kaplan-Meier were 95% and 87.5%, respectively. The total 3-year cost for patients treated in the desensitization arm was $219,914 per patient compared with $238,667 per patient treated in the dialysis arm. Thus, each patient treated with desensitization is estimated to save the U.S. healthcare system $18,753 in 2011 USD. Overall, estimated patient survival at the end of 3 years was 96.6% for patients in the desensitization arm of the model (based on Cedars-Sinai survival rate) compared with 79.0% for an age, end-stage renal disease etiology, and PRA matched group of patients remaining on dialysis during the study period. We conclude that desensitization with IVIG+rituximab is clinically and cost-effective, with both financial savings and an estimated 17.6% greater probability of 3-year survival associated with desensitization versus dialysis alone. However, the benefits of desensitization and transplantation are limited by organ availability and allocation policies.

Development of [{sup 62}Zn/{sup 62}Cu]-DOTA-rituximab as a possible novel in vivo PET generator for anti-CD20 antigen imaging

Energy Technology Data Exchange (ETDEWEB)

Gholipour, Nazila [Tehran University of Medical Sciences, Tehran (Iran, Islamic Republic of). Dept. of Radiopharmacy; Jalilian, Amir R.; Fazaeli, Yousef; Moradkhani, Sedigheh; Bolourinovin, Fateme [Nuclear Science and Technology Research Institute (NSTRI), Tehran (Iran, Islamic Republic of); Sabzevari, Omid [Tehran University of Medical Sciences, Tehran (Iran, Islamic Republic of). Dept. of Toxicology and Pharmacology; Khalaj, Ali [Tehran University of Medical Sciences, Tehran (Iran, Islamic Republic of). Dept. of Medical Chemistry

2014-07-01

In this study, zinc-62 was prepared at radiopharmaceutical grade (for {sup 62}Zn/{sup 62}Cu generator production) using {sup nat}Cu(p, xn) reaction with the production yield of 5.9 mCi/μAh at 30 MeV proton energy (radiochemical separation yield >95%, radionuclidic purity >99% and radiochemical purity >99%). In the next step, rituximab was successively labeled with [{sup 62}Zn]-ZnCl{sub 2} after conjugation with p-SCN-Bz-DOTA followed by molecular filtration and determination of the average number of DOTA conjugated per mAb (6:1) by spectrophotometric method. Radiochemical purity (>97%, measured by ITLC and HPLC), integrity of protein after radiolabeling (gel electrophoresis) and stability of [{sup 62}Zn]-DOTA-rituximab (in final formulation, and human serum) were determined 1-8 h as well as biodistribution studies in wild-type rats followed by coincidence imaging for 6 h. However, the accumulation of the radiolabeled antibody was not consistent with the former reported rituximab conjugates. [{sup 62}Zn]-labeled monoclonal antibodies and fragments can be prepared as potential in vivo PET generators for molecular imaging however, the search for application of stable zinc complexes must be continued.

The value of rituximab treatment in primary Sjögren's syndrome

NARCIS (Netherlands)

Verstappen, Gwenny M.; van Nimwegen, Jolien F.; Vissink, Arjan; Kroese, Frans G. M.; Bootsma, Hendrika

The rationale for B cell depletion therapy with rituximab in primary Sjogren's syndrome relies upon the well-established role of B cell hyperactivity in immunopathogenesis. In line with this notion, several biomarkers of B cell activity are significantly affected by treatment, both in the target

Radioimmunotherapy using 131I-rituximab in patients with advanced stage B-cell non-Hodgkin's lymphoma: initial experience

International Nuclear Information System (INIS)

Bienert, Maren; Reisinger, Ingrid; Humplik, Beatrice I.; Reim, Christel; Kroessin, Thomas; Avril, Norbert; Munz, Dieter L.; Srock, Stefanie; Pezzutto, Antonio

2005-01-01

The aim of this study was to evaluate the safety, toxicity and therapeutic response of non-myeloablative radioimmunotherapy using 131 I-rituximab in previously heavily treated patients with B-cell non-Hodgkin's lymphoma (B-NHL). Nine patients with relapsed, refractory or transformed B-NHL received ten radioimmunotherapies. Patients had a median of 5 (range 2-7) prior standard therapies. Four patients had received prior high-dose chemotherapy followed by autologous stem cell transplantation, and eight had received prior rituximab therapy. Histopathology consisted of four mantle cell, one follicular and four diffuse large B-cell lymphomas. Rituximab, a monoclonal chimeric anti-CD20 antibody (IDEC-C2B8), was labelled with 131 I using the Iodogen method. The administered activity (2,200±600 MBq) was based on a dosimetrically calculated 45 cGy total-body radiation dose. All patients received an infusion of 2.5 mg/kg of rituximab prior to administration of the radiopharmaceutical. No acute adverse effects were observed after the administration of 131 I-rituximab. Radioimmunotherapy was safe in our patient group and achieved one complete response ongoing at 14 months and two partial responses progressing at 12 and 13 months after treatment. One partial responder was re-treated with radioimmunotherapy and achieved an additional progression-free interval of 7 months. Four non-responders with bulky disease died 4.8±2.0 months after therapy. Three patients had an elevated serum lactate dehydrogenase (LDH) level prior to radioimmunotherapy and none of the patients responded. Of two patients who received radioimmunotherapy as an additional treatment after salvage chemotherapy, one continues to be disease-free at 9 months and one relapsed at 5 months' follow-up. Reversible grade 3 or 4 haematological toxicity occurred in seven of nine patients. Median nadirs were 35 days for platelets, 44 days for leucocytes and 57 days for erythrocytes. (orig.)

Refractory myasthenia gravis - clinical profile, comorbidities and response to rituximab.

Science.gov (United States)

Sudulagunta, Sreenivasa Rao; Sepehrar, Mona; Sodalagunta, Mahesh Babu; Settikere Nataraju, Aravinda; Bangalore Raja, Shiva Kumar; Sathyanarayana, Deepak; Gummadi, Siddharth; Burra, Hemanth Kumar

2016-01-01

Introduction: Myasthenia gravis (MG) is an antibody mediated autoimmune neuromuscular disorder characterized by fatigable muscle weakness. A proportion of myasthenia gravis patients are classified as refractory due to non responsiveness to conventional treatment. This retrospective study was done to evaluate clinical profile, epidemiological, laboratory, and features of patients with MG and mode of management using rituximab and complications. Methods: Data of myasthenia gravis patients admitted or presented to outpatient department (previous medical records) with MG between January 2008 and January 2016 were included. A total of 512 patients fulfilled the clinical and diagnostic criteria of myasthenia gravis of which 76 patients met the diagnostic certainty for refractory myasthenia gravis and were evaluated. Results: Out of 76 refractory MG patients, 53 (69.73%) patients fulfilled all the three defined criteria. The median age of onset of the refractory MG group was 36 years with a range of 27-53 years. In our study 25 patients (32.89%) belonged to the age group of 21-30 years. Anti-MuSK antibodies were positive in 8 non-refractory MG patients (2.06%) and 36 refractory MG patients (47.36%). Mean HbA 1C was found to be 8.6±2.33. The dose of administered prednisone decreased by a mean of 59.7% ( p =3.3x10 -8 ) to 94.6% ( p =2.2x10 -14 ) after the third cycle of rituximab treatment. Conclusion: The refractory MG patients are most commonly female with an early age of onset, anti-MuSK antibodies, and thymomas. Refractory MG patients have higher prevalence and poor control (HbA 1C >8%) of diabetes mellitus and dyslipidemia probably due to increased steroid usage. Rituximab is very efficient in treatment of refractory MG with adverse effects being low.

Leuconostoc sp. Meningitis in a Patient Treated with Rituximab for Mantle Cell Lymphoma

Directory of Open Access Journals (Sweden)

Hrvoje Holik

2015-09-01

Full Text Available We present a 64-year-old man who was treated with R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisolone chemoimmunotherapy for mantle cell lymphoma and developed purulent meningitis, probably caused by Leuconostoc sp. The patient had severe hypogammaglobulinemia, which is a possible complication of rituximab therapy. To our knowledge and after reviewing the available medical literature, this is the first described case of purulent meningitis caused by Leuconostoc sp. in a patient with mantle cell lymphoma that appeared after treatment with the R-CHOP protocol. The diagnosis of purulent meningitis was based on clinical, laboratory and cytological cerebrospinal fluid findings, in addition to blood culture results in which we isolated Leuconostoc sp. The patient was treated with meropenem with full recovery.

Radiolabeling of rituximab with 188Re and 99mTc using the tricarbonyl technology

International Nuclear Information System (INIS)

Dias, Carla Roberta; Jeger, Simone; Osso, Joao Alberto; Mueller, Cristina; De Pasquale, Christine; Hohn, Alexander; Waibel, Robert; Schibli, Roger

2011-01-01

Introduction: The most successful clinical studies of immunotherapy in patients with non-Hodgkin's lymphoma (NHL) use the antibody rituximab (RTX) targeting CD20 + B-cell tumors. Rituximab radiolabeled with β - emitters could potentiate the therapeutic efficacy of the antibody by virtue of the particle radiation. Here, we report on a direct radiolabeling approach of rituximab with the 99m Tc- and 188 Re-tricarbonyl core (IsoLink technology). Methods: The native format of the antibody (RTX wt ) as well as a reduced form (RTX red ) was labeled with 99m Tc/ 188 Re(CO) 3 . The partial reduction of the disulfide bonds to produce free sulfhydryl groups (-SH) was achieved with 2-mercaptoethanol. Radiolabeling efficiency, in vitro human plasma stability as well as transchelation toward cysteine and histidine was investigated. The immunoreactivity and binding affinity were determined on Ramos and/or Raji cells expressing CD20. Biodistribution was performed in mice bearing subcutaneous Ramos lymphoma xenografts. Results: The radiolabeling efficiency and kinetics of RTX red were superior to that of RTX wt ( 99m Tc: 98% after 3 h for RTX red vs. 70% after 24 h for RTX wt ). 99m Tc(CO) 3 -RTX red was used without purification for in vitro and in vivo studies whereas 188 Re(CO) 3 -RTX red was purified to eliminate free 188 Re-precursor. Both radioimmunoconjugates were stable in human plasma for 24 h at 37 o C. In contrast, displacement experiments with excess cysteine/histidine showed significant transchelation in the case of 99m Tc(CO) 3 -RTX red but not with pre-purified 188 Re(CO) 3 -RTX red . Both conjugates revealed high binding affinity to the CD20 antigen (K d =5-6 nM). Tumor uptake of 188 Re(CO) 3 -RTX red was 2.5 %ID/g and 0.8 %ID/g for 99m Tc(CO) 3 -RTX red 48 h after injection. The values for other organs and tissues were similar for both compounds, for example the tumor-to-blood and tumor-to-liver ratios were 0.4 and 0.3 for 99m Tc(CO) 3 -RTX red and for 188 Re

Remission Achieved in Refractory Advanced Takayasu Arteritis Using Rituximab

Directory of Open Access Journals (Sweden)

D. Ernst

2012-01-01

Full Text Available A 25-year-old patient was referred due to subclavian stenosis, identified on echocardiography. She presented with exertional dizziness and dyspnoea. Questioning revealed bilateral arm claudication. Examination demonstrated an absent right ulnar pulse and asymmetrical brachial blood pressure. Bruits were evident over both common carotid arteries. Doppler ultrasound and MRI angiograms revealed occlusion or stenosis in multiple large arteries. Takayasu arteritis (TA was diagnosed and induction therapy commenced: 1 mg/kg oral prednisolone and 500 mg/m2 intravenous cyclophosphamide (CYC. Attempts to reduce prednisolone below 15 mg/d proved impossible due to recurring disease activity. Adjuvant azathioprine 100 mg/d was subsequently added. Several weeks later, the patient was admitted with a left homonymous hemianopia. The culprit lesion in the right carotid artery was surgically managed and the patient discharged on azathioprine 150 mg/d and prednisolone 30 mg/d. Despite this, deteriorating exertional dyspnoea and angina pectoris were reported. Reimaging confirmed new stenosis in the right pulmonary artery. Surgical treatment proved infeasible. Given evidence of refractory disease activity on maximal standard therapy, we initiated rituximab, based on recently reported B-cell activity in TA.

Internalization of rituximab and the efficiency of B Cell depletion in rheumatoid arthritis and systemic lupus erythematosus.

Science.gov (United States)

Reddy, Venkat; Cambridge, Geraldine; Isenberg, David A; Glennie, Martin J; Cragg, Mark S; Leandro, Maria

2015-05-01

Rituximab, a type I anti-CD20 monoclonal antibody (mAb), induces incomplete B cell depletion in some patients with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE), thus contributing to a poor clinical response. The mechanisms of this resistance remain elusive. The purpose of this study was to determine whether type II mAb are more efficient than type I mAb at depleting B cells from RA and SLE patients, whether internalization influences the efficiency of depletion, and whether Fcγ receptor type IIb (FcγRIIb) and the B cell receptor regulate this internalization process. We used an in vitro whole blood B cell-depletion assay to assess the efficiency of depletion, flow cytometry to study cell surface protein expression, and surface fluorescence-quenching assays to assess rituximab internalization, in samples from patients with RA and patients with SLE. Paired t-test or Mann-Whitney U test was used to compare groups, and Spearman's rank correlation test was used to assess correlation. We found that type II mAb internalized significantly less rituximab than type I mAb and depleted B cells from patients with RA and SLE at least 2-fold more efficiently than type I mAb. Internalization of rituximab was highly variable between patients, was regulated by FcγRIIb, and inversely correlated with cytotoxicity in whole blood B cell-depletion assays. The lowest levels of internalization were seen in IgD- B cells, including postswitched (IgD-CD27+) memory cells. Internalization of type I anti-CD20 mAb was also partially inhibited by anti-IgM stimulation. Variability in internalization of rituximab was observed and was correlated with impaired B cell depletion. Therefore, slower-internalizing type II mAb should be considered as alternative B cell-depleting agents for the treatment of RA and SLE. © 2015 The Authors. Arthritis & Rheumatology is published by Wiley Periodicals, Inc. on behalf of the American College of Rheumatology.

[Efficacy and safety of rituximab in the treatment of primary antiphospholipid syndrome: analysis of 24 cases from the bibliography review].

Science.gov (United States)

Pons, Isaac; Espinosa, Gerard; Cervera, Ricard

2015-02-02

Antiphospholipid syndrome (APS) is characterized by the presence of antiphospholipid antibodies (aPL) and thrombotic and/or obstetric manifestations. Patients without another associated autoimmune disease are considered to have primary APS. Some patients develop thrombosis recurrence despite anticoagulant treatment and some clinical features do not respond to standard therapy. Rituximab may be an alternative in these cases. We review the published scientific evidence on the use of rituximab in the treatment of primary APS. Description of a case and review of the literature with descriptive analysis of the demographic, clinical, and immunologic features, treatment and outcome of patients. We identified 24 patients (15 women [62.5%]), with a mean age of 37.0 ± 13.4 years. The reasons for the use of rituximab were thrombocytopenia (41.7%), skin involvement (33.3%), neurologic and heart valve involvement (12.5%), hemolytic anemia (8.3%) and pulmonary and renal involvement (4.2%). Lupus anticoagulant was present in 72.7% of the cases, the IgG and IgM isotypes of anticardiolipin antibodies in 75 and 50%, respectively, and the anti-β2GPI (IgG e IgM) antibodies in 80% of patients. Thirteen (54.1%) patients received 2 doses of 1,000 mg of rituximab fortnightly, 10 (41.7%) 4 doses of 375 mg/m(2) weekly and one (4.2%) 8 doses of 375 mg/m(2) weekly. Eleven (45.8%) patients presented a complete clinical response, 7 (29.2%) a partial response and 6 (25%) did not respond to rituximab. Four patients with clinical improvement presented with aPL titer decrease and in one patient, aPL levels did not change. In one patient without clinical response, aPL remained positive. A clinical-immunologic dissociation existed in 2 additional cases. The results obtained suggest a possible potential benefit of rituximab in the treatment of some clinical manifestations of primary APS such as thrombocytopenia, skin and heart valve involvement. Copyright © 2013 Elsevier España, S.L.U. All rights

First-line chemoimmunotherapy with bendamustine and rituximab versus fludarabine, cyclophosphamide, and rituximab in patients with advanced chronic lymphocytic leukaemia (CLL10)

DEFF Research Database (Denmark)

Eichhorst, Barbara; Fink, Anna-Maria; Bahlo, Jasmin

2016-01-01

BACKGROUND: Chemoimmunotherapy with fludarabine, cyclophosphamide, and rituximab is the standard therapy for physically fit patients with advanced chronic lymphocytic leukaemia. This international phase 3 study compared the efficacy and tolerance of the standard therapy with a potentially less....... The final analysis was done by intention to treat. The study is registered with ClinicalTrials.gov, number NCT%2000769522. FINDINGS: 688 patients were recruited between Oct 2, 2008, and July 11, 2011, of which 564 patients who met inclusion criteria were randomly assigned. 561 patients were included...

Refractory myasthenia gravis – clinical profile, comorbidities and response to rituximab

Science.gov (United States)

Sudulagunta, Sreenivasa Rao; Sepehrar, Mona; Sodalagunta, Mahesh Babu; Settikere Nataraju, Aravinda; Bangalore Raja, Shiva Kumar; Sathyanarayana, Deepak; Gummadi, Siddharth; Burra, Hemanth Kumar

2016-01-01

Introduction: Myasthenia gravis (MG) is an antibody mediated autoimmune neuromuscular disorder characterized by fatigable muscle weakness. A proportion of myasthenia gravis patients are classified as refractory due to non responsiveness to conventional treatment. This retrospective study was done to evaluate clinical profile, epidemiological, laboratory, and features of patients with MG and mode of management using rituximab and complications. Methods: Data of myasthenia gravis patients admitted or presented to outpatient department (previous medical records) with MG between January 2008 and January 2016 were included. A total of 512 patients fulfilled the clinical and diagnostic criteria of myasthenia gravis of which 76 patients met the diagnostic certainty for refractory myasthenia gravis and were evaluated. Results: Out of 76 refractory MG patients, 53 (69.73%) patients fulfilled all the three defined criteria. The median age of onset of the refractory MG group was 36 years with a range of 27–53 years. In our study 25 patients (32.89%) belonged to the age group of 21–30 years. Anti-MuSK antibodies were positive in 8 non-refractory MG patients (2.06%) and 36 refractory MG patients (47.36%). Mean HbA1C was found to be 8.6±2.33. The dose of administered prednisone decreased by a mean of 59.7% (p=3.3x10–8) to 94.6% (p=2.2x10–14) after the third cycle of rituximab treatment. Conclusion: The refractory MG patients are most commonly female with an early age of onset, anti-MuSK antibodies, and thymomas. Refractory MG patients have higher prevalence and poor control (HbA1C >8%) of diabetes mellitus and dyslipidemia probably due to increased steroid usage. Rituximab is very efficient in treatment of refractory MG with adverse effects being low. PMID:27790079

Correction to: Progressive multifocal leukoencephalopathy in rituximab-treated rheumatic diseases: a rare event.

Science.gov (United States)

Berger, Joseph R; Malik, Vineeta; Lacey, Stuart; Brunetta, Paul; Lehane, Patricia B

2018-04-10

The article "Progressive multifocal leukoencephalopathy in rituximab-treated rheumatic diseases: a rare event," written by Joseph R. Berger, Vineeta Malik, Stuart Lacey, Paul Brunetta, and Patricia B. Lehane 3 , was originally published electronically on the publisher's internet portal (currently SpringerLink).

Radiolabeling parameters of 177Lu-DOTA-RITUXIMAB

International Nuclear Information System (INIS)

Massicano, Adriana V.F.; Alcarde, Lais F.; Oliveira, Ricardo S.; Mengatti, Jair; Araujo, Elaine B. de

2013-01-01

Cancer treatment using radioimmunotherapy (RIT) has been the focus of much research in the last two decades. In RIT, a radioisotope is coupled to a monoclonal antibody (mAb) to form a tumor-specific target agent to improve the cytocidal effect of the mAbs. RIT allows the systemic delivery of radiation to disease target by mAbs while sparing normal tissues. Rituximab® (Mabthera - Roche) is a chimeric mouse-human monoclonal antibody; it selectively binds with high affinity to the CD20 antigen, a hydrophobic transmembrane protein, which is expressed on B-lymphocytes and in more than 90% of B cell non-Hodgkin's lymphomas (NHL). The conjugation and radiolabeling process involve special conditions of pH and temperature, long processes of manipulation and mixing. All this process can damage the antibody structure and compromise its clinical application. Therefore, these parameters must be largely studied. The aim of this work was to evaluate the best radiolabeling conditions of DOTA-rituximab. Briefly, 10 mg of antibody previously purified by ultrafiltration device was conjugated with DOTA-NHS-ester (Macrocyclics) in 50 fold molar excess. The reaction was conducted for 1 hour in phosphate buffer pH 8.0 and gently mixing at room temperature, remaining for 24 hours under refrigeration. The immunoconjugated was purified by size exclusion column and ultrafiltration device. The radiolabeled parameters studied were: immunoconjugated mass, activity of 177 LuCl 3 , reaction time, temperature and pH. The radiochemical purity of the preparations was determined using analysis by thin layer chromatography (TLC-SG plates). The best studied condition presented radiochemical purity above 95% and the integrity of antibody was preserved. (author)

[Bendamustine-rituximab therapy is effective for transformed follicular lymphoma with significant expression of p53].

Science.gov (United States)

Kuroda, Hiroyuki; Jomen, Wataru; Miura, Shogo; Arihara, Yohei; Yamada, Michiko; Hirako, Tasuku; Abe, Tomoyuki; Sakurai, Tamaki; Fujii, Shigeyuki; Maeda, Masahiro; Fujita, Miri; Nagashima, Kazuo; Okagawa, Yutaka; Hoki, Toshifumi; Kato, Junji

2013-08-01

We describe a patient with transformed follicular lymphoma(FL), expressing p53 but remaining in complete remission(CR) due to bendamustine-rituximab(BR)therapy. She was a 64-year-old female diagnosed with stage IV FL(grade 3A)in July 2007 when she was admitted with right lower abdominal pain and body weight loss. Colonoscopy revealed Bauhin' valve lymphoma of the terminal ileum, and computed tomography(CT)scan showed lymphadenopathy, involving the cervical, mediastinal para-aortic lymph nodes and right tonsil. She received chemotherapy with eight courses of CHOP therapy with rituximab and achieved CR. Two and a half years later, mediastinal lymph node swelling relapsed, and ibritumomab tiuxetan therapy induced the second CR. After ten months, however, a third relapse occurred as a submucosal tumor(SMT)of the stomach. Gastric SMT biopsy showed diffuse large B cell lymphoma(DLBCL)transformation with immunohistochemical expression of p53. Although gastric SMT disappeared after radiotherapy, which achieved the third CR, lymph node swelling was detected again in the para-aortic and-iliac artery lymph nodes in September 2011. Subsequently, she was treated with five courses of BR therapy, because bendamustine had been reported to be effective for p53 gene-deficient B cell neoplasms. The therapy was successful and achieved the fourth CR, demonstrating that BR therapy was effective for p53-expressing DLBCL.

Response to rituximab in a refractory case of thrombotic thrombocytopenic purpura associated with systemic lupus erythematosus

Directory of Open Access Journals (Sweden)

Niaz Faraz

2010-01-01

Full Text Available Thrombotic thrombocytopenic purpura (TTP is a serious disorder with a significant morbidity and mortality. Majority of cases of TTP are idiopathic, but some cases may be secon-dary to connective tissue diseases. TTP has been rarely associated with systemic lupus erythe-matosus (SLE and may be refractory to treatment with plasma exchange, requiring immuno-suppressive therapy. We describe a patient with TTP and SLE who was refractory to plasma exchange and corticosteroids but responded to anti-CD20 antibody rituximab with continued re-mission after eight months of follow-up. Rituximab appears to be an effective treatment in re-fractory cases of TTP associated with SLE.

Systemic adverse events following rituximab therapy in patients with Graves' disease

DEFF Research Database (Denmark)

El Fassi, D; Nielsen, C H; Junker, P

2010-01-01

had the third highest increase in immunoglobulin deposition on monocytes by day 14. The arthralgias persisted in two of the patients, despite glucocorticoid rescue therapy. Conclusions: We report articular adverse events in three and gastrointestinal symptoms in two out of ten GD patients who received...... methimazole only. Adverse events were recorded, and the presence of circulating immune complexes (CICs) was measured as IgG, IgM and complement component 3 (C3) depositing on normal monocytes following incubation with patient plasma. Results: Five patients had benign infusion-related adverse events at first......Background and aim: Rituximab (RTX) therapy has shown promising results in Graves´ disease (GD), with or without ophthalmopathy. We examined the occurrence of adverse events in GD patients treated with RTX. Subjects and methods: Ten patients received RTX and methimazole, while ten patients received...

Rituximab for childhood-onset, complicated, frequently relapsing nephrotic syndrome or steroid-dependent nephrotic syndrome: a multicentre, double-blind, randomised, placebo-controlled trial.

Science.gov (United States)

Iijima, Kazumoto; Sako, Mayumi; Nozu, Kandai; Mori, Rintaro; Tuchida, Nao; Kamei, Koichi; Miura, Kenichiro; Aya, Kunihiko; Nakanishi, Koichi; Ohtomo, Yoshiyuki; Takahashi, Shori; Tanaka, Ryojiro; Kaito, Hiroshi; Nakamura, Hidefumi; Ishikura, Kenji; Ito, Shuichi; Ohashi, Yasuo

2014-10-04

Rituximab could be an effective treatment for childhood-onset, complicated, frequently relapsing nephrotic syndrome (FRNS) and steroid-dependent nephrotic syndrome (SDNS). We investigated the efficacy and safety of rituximab in patients with high disease activity. We did a multicentre, double-blind, randomised, placebo-controlled trial at nine centres in Japan. We screened patients aged 2 years or older experiencing a relapse of FRNS or SDNS, which had originally been diagnosed as nephrotic syndrome when aged 1-18 years. Patients with complicated FRNS or SDNS who met all other criteria were eligible for inclusion after remission of the relapse at screening. We used a computer-generated sequence to randomly assign patients (1:1) to receive rituximab (375 mg/m(2)) or placebo once weekly for 4 weeks, with age, institution, treatment history, and the intervals between the previous three relapses as adjustment factors. Patients, guardians, caregivers, physicians, and individuals assessing outcomes were masked to assignments. All patients received standard steroid treatment for the relapse at screening and stopped taking immunosuppressive agents by 169 days after randomisation. Patients were followed up for 1 year. The primary endpoint was the relapse-free period. Safety endpoints were frequency and severity of adverse events. Patients who received their assigned intervention were included in analyses. This trial is registered with the University Hospital Medical Information Network clinical trials registry, number UMIN000001405. Patients were centrally registered between Nov 13, 2008, and May 19, 2010. Of 52 patients who underwent randomisation, 48 received the assigned intervention (24 were given rituximab and 24 placebo). The median relapse-free period was significantly longer in the rituximab group (267 days, 95% CI 223-374) than in the placebo group (101 days, 70-155; hazard ratio: 0·27, 0·14-0·53; p<0·0001). Ten patients (42%) in the rituximab group and six (25

Treatment of Graves' disease with rituximab specifically reduces the production of thyroid stimulating autoantibodies

DEFF Research Database (Denmark)

El Fassi, Daniel; Banga, J Paul; Gilbert, Jacqueline A

2008-01-01

involving Chinese hamster ovary cells transfected with the human thyrotropin receptor, we found that the stimulatory capacity of TRAbs was reduced markedly, by 66+/-22%, upon treatment with rituximab and methimazole for 21 days (p

Radioimmunotherapy in refractory b-cell nonhodgkins lymphoma with I-131-labeled chimeric anti cd-20 c2b8 (I-131 rituximab): preliminary result

International Nuclear Information System (INIS)

Kang, Hye Jin; Park, Yeon Hee; Kim, Sung Eun and others

2005-01-01

Recently, the native chimeric human-mouse anti CD-20 antibody IDEC-C2B8 (Rituximab) has been widely applied in NHL. This ongoing phase study was to evaluate whether radioimmunotherapy (RIT) with I-131 rituximab is effective in refractory B-cell NHL. Inclusion criteria were as follows: B-cell NHL with relapsed or refractory to primary standard therapy, measurable disease, adequate hematologic, renal, and hepatic function, informed consent. The rituximab (Mabthera, Roach) was radiolabeled with iodine-131(I-131) using a modified chloramine T method with high radiochemical purity (95%) and preservation of immuno-reactivity. All patients received loading doses of unlabeled rituximab (median, 40 mg: range, 20∼70 mg) immediately prior to administration of therapeutic dose (51.4∼152.2 MBq/kg), and then underwent gamma camera scan. 11 patients were enrolled (4 low-grade B-cell NHL, 7 DLBCL, median age 63 years). Patients had received a median of three prior chemotherapy regimens. The objective response rate was 36.4% (1 CR, 3 PRs). These all responses were observed in low-grade B-cell NHL, except one with DLBCL. Adverse events were primarily hematologic toxicities; the incidence of grade 3/4 neutropenia, thrombocytopenia, and anemia was 27.3%, 45.5%, and 18.2%, respectively. The treatment-related mortality was observed in one patient, who had been previously treated with high-dose chemotherapy plus TBI with autologous stem cell transplantation. RIT with I-131 rituximab seems to be effective tolerable in refractory low-grade B-cell NHL, although modest activity in refractory DLBCL. Further studies to define the efficacy of I-131 rituximab in DLBCL are warranted

Radioimmunotherapy in refractory b-cell nonhodgkins lymphoma with I-131-labeled chimeric anti cd-20 c2b8 (I-131 rituximab): preliminary result

Energy Technology Data Exchange (ETDEWEB)

Kang, Hye Jin; Park, Yeon Hee; Kim, Sung Eun and others [Korea University Medical School, Seoul (Korea, Republic of)

2005-07-01

Recently, the native chimeric human-mouse anti CD-20 antibody IDEC-C2B8 (Rituximab) has been widely applied in NHL. This ongoing phase study was to evaluate whether radioimmunotherapy (RIT) with I-131 rituximab is effective in refractory B-cell NHL. Inclusion criteria were as follows: B-cell NHL with relapsed or refractory to primary standard therapy, measurable disease, adequate hematologic, renal, and hepatic function, informed consent. The rituximab (Mabthera, Roach) was radiolabeled with iodine-131(I-131) using a modified chloramine T method with high radiochemical purity (95%) and preservation of immuno-reactivity. All patients received loading doses of unlabeled rituximab (median, 40 mg: range, 20{approx}70 mg) immediately prior to administration of therapeutic dose (51.4{approx}152.2 MBq/kg), and then underwent gamma camera scan. 11 patients were enrolled (4 low-grade B-cell NHL, 7 DLBCL, median age 63 years). Patients had received a median of three prior chemotherapy regimens. The objective response rate was 36.4% (1 CR, 3 PRs). These all responses were observed in low-grade B-cell NHL, except one with DLBCL. Adverse events were primarily hematologic toxicities; the incidence of grade 3/4 neutropenia, thrombocytopenia, and anemia was 27.3%, 45.5%, and 18.2%, respectively. The treatment-related mortality was observed in one patient, who had been previously treated with high-dose chemotherapy plus TBI with autologous stem cell transplantation. RIT with I-131 rituximab seems to be effective tolerable in refractory low-grade B-cell NHL, although modest activity in refractory DLBCL. Further studies to define the efficacy of I-131 rituximab in DLBCL are warranted.

Persistence and selection of an expanded B-cell clone in the setting of rituximab therapy for Sjögren's syndrome.

Science.gov (United States)

Hershberg, Uri; Meng, Wenzhao; Zhang, Bochao; Haff, Nancy; St Clair, E William; Cohen, Philip L; McNair, Patrice D; Li, Ling; Levesque, Marc C; Luning Prak, Eline T

2014-02-11

Subjects with primary Sjögren's syndrome (SjS) have an increased risk of developing B-cell lymphoma and may harbor monoclonal B-cell expansions in the peripheral blood. Expanded B-cell clones could be pathogenic, and their persistence could exacerbate disease or predispose toward the development of lymphoma. Therapy with anti-CD20 (rituximab) has the potential to eliminate expanded B-cell clones and thereby potentially ameliorate disease. This study was undertaken to identify and track expanded B-cell clones in the blood of subjects with primary SjS who were treated with rituximab. To determine whether circulating B-cell clones in subjects with primary SjS emerge or remain after B cell-depleting therapy with rituximab, we studied the antibody heavy-chain repertoire. We performed single-memory B-cell and plasmablast sorting and antibody heavy-chain sequencing in six rituximab-treated SjS subjects over the course of a 1-year follow-up period. Expanded B-cell clones were identified in four out of the six rituximab-treated SjS subjects, based upon the independent amplification of sequences with identical or highly similar VH, DH, and JH gene segments. We identified one SjS subject with a large expanded B-cell clone that was present prior to therapy and persisted after therapy. Somatic mutations in the clone were numerous but did not increase in frequency over the course of the 1-year follow-up, suggesting that the clone had been present for a long period of time. Intriguingly, a majority of the somatic mutations in the clone were silent, suggesting that the clone was under chronic negative selection. For some subjects with primary SjS, these data show that (a) expanded B-cell clones are readily identified in the peripheral blood, (b) some clones are not eliminated by rituximab, and (c) persistent clones may be under chronic negative selection or may not be antigen-driven. The analysis of sequence variation among members of an expanded clone may provide a novel means

Rituximab-containing reduced-intensity conditioning improves progression-free survival following allogeneic transplantation in B cell non-Hodgkin lymphoma

Directory of Open Access Journals (Sweden)

Narendranath Epperla

2017-06-01

Full Text Available Abstract Background In B cell non-Hodgkin lymphoma (B-NHL, rituximab-containing reduced-intensity conditioning regimens (R-RIC have been shown to provide favorable outcomes in single-arm studies; however, large multicenter studies comparing R-RIC and non-rituximab-containing reduced-intensity conditioning regimens (nonR-RIC have not been performed. Using the CIBMTR database, we report the outcomes of R-RIC versus nonR-RIC regimens in B-NHL. Methods We evaluated 1401 adult B-NHL patients undergoing allogeneic hematopoietic cell transplantation (allo-HCT who received nonR-RIC (n = 1022 or R-RIC (n = 379 regimens. Graft-versus-host disease (GVHD prophylaxis was limited to calcineurin inhibitor-based approaches. Results Median follow-up of survivors in the R-RIC and nonR-RIC groups was 47 and 37 months, respectively. On multivariate analysis, no difference was seen between the R-RIC and nonR-RIC cohorts in terms of acute GVHD grade II–IV (RR = 1.14, 95%CI = 0.83–1.56, p = 0.43 or grade III–IV (RR = 1.16, 95%CI = 0.72–1.89, p = 0.54, chronic GVHD (RR = 1.15, 95%CI = 0.92–1.46, p = 0.22, non-relapse mortality (RR = 0.90; 95%CI = 0.67–1.22; p = 0.51, relapse/progression (RR = 0.79; 95%CI = 0.63–1.01; p = 0.055, and mortality (RR = 0.84, 95%CI = 0.69–1.02, p = 0.08 risk. However, R-RIC was associated with a significantly improved progression-free survival (RR = 0.76; 95%CI 0.62–0.92; p = 0.006. On subgroup analysis, mortality benefit was noted in the R-RIC group patients not receiving busulfan-based RIC (RR = 0.76; 95%CI = 0.60–0.96; p = 0.02 and with the use of a higher cumulative rituximab dose (RR = 0.43; 95%CI = 0.21–0.90; p = 0.02. Conclusion Our analysis shows that inclusion of rituximab in RIC regimens improves progression-free survival in patients with B cell NHL. These data supports the use of R-RIC in B

Activatory and Inhibitory Fcγ Receptors Augment Rituximab-mediated Internalization of CD20 Independent of Signaling via the Cytoplasmic Domain*

Science.gov (United States)

Vaughan, Andrew T.; Chan, Claude H. T.; Klein, Christian; Glennie, Martin J.; Beers, Stephen A.; Cragg, Mark S.

2015-01-01

Type I anti-CD20 mAb such as rituximab and ofatumumab engage with the inhibitory FcγR, FcγRIIb on the surface of B cells, resulting in immunoreceptor tyrosine-based inhibitory motif (ITIM) phosphorylation. Internalization of the CD20·mAb·FcγRIIb complex follows, the rate of which correlates with FcγRIIb expression. In contrast, although type II anti-CD20 mAb such as tositumomab and obinutuzumab also interact with and activate FcγRIIb, this interaction fails to augment the rate of CD20·mAb internalization, raising the question of whether ITIM phosphorylation plays any role in this process. We have assessed the molecular requirements for the internalization process and demonstrate that in contrast to internalization of IgG immune complexes, FcγRIIb-augmented internalization of rituximab-ligated CD20 occurs independently of the FcγRIIb ITIM, indicating that signaling downstream of FcγRIIb is not required. In transfected cells, activatory FcγRI, FcγRIIa, and FcγRIIIa augmented internalization of rituximab-ligated CD20 in a similar manner. However, FcγRIIa mediated a slower rate of internalization than cells expressing equivalent levels of the highly homologous FcγRIIb. The difference was maintained in cells expressing FcγRIIa and FcγRIIb lacking cytoplasmic domains and in which the transmembrane domains had been exchanged. This difference may be due to increased degradation of FcγRIIa, which traffics to lysosomes independently of rituximab. We conclude that the cytoplasmic domain of FcγR is not required for promoting internalization of rituximab-ligated CD20. Instead, we propose that FcγR provides a structural role in augmenting endocytosis that differs from that employed during the endocytosis of immune complexes. PMID:25568316

Launching biosimilar rituximab: an industry opinion on biosimilar uptake in Europe.

Science.gov (United States)

Trollope, Richard; Johnson, Sue; Ireland, Henry

2017-06-01

Richard Trollope and Sue Johnson talk with Henry Ireland, Senior Editor about the recent approval of biosimilar rituximab (Truxima ® ) & the current state of biosimilar uptake across Europe Richard Trollope, Head of Biosimilars, Mundipharma International Limited, qualified as a biochemist before joining Wyeth's commercial operations, prior to its acquisition by Pfizer. Richard later joined Yamanouchi Pharmaceuticals (now Astellas Pharma). His fascination with oncology led him to join Mundipharma in Europe and after joining the company's UK arm (Napp Pharmaceuticals Limited), Richard began his journey in biosimilars. He now heads up the biosimilar franchise at Mundipharma International as it launches biosimilar rituximab (Truxima ® ) - the first biosimilar monoclonal antibody for the treatment of cancer, which will be distributed by Napp Pharmaceuticals in the UK. Sue Johnson, PhD, Medical Insights at Mundipharma International Limited, is a scientist by background and completed her postdoc fellowship at Harvard Medical School. On returning to the UK, she began her career in the pharmaceutical industry, working in UK Medical Affairs before transitioning to a European role with Mundipharma 2 years ago, where she leads on Medical Insights for the biosimilars franchise.

Rituximab is associated with improved survival in Burkitt lymphoma: a retrospective analysis from two US academic medical centers.

Science.gov (United States)

Wildes, Tanya M; Farrington, Laura; Yeung, Cecilia; Harrington, Alexandra M; Foyil, Kelley V; Liu, Jingxia; Kreisel, Friederike; Bartlett, Nancy L; Fenske, Timothy S

2014-02-01

Burkitt lymphoma (BL) is a rare, highly aggressive B-cell malignancy treated most successfully with brief-duration, high-intensity chemotherapeutic regimens. The benefit of the addition of rituximab to these regimens remains uncertain. We sought to examine the effectiveness of chemotherapy with and without rituximab in patients with BL. This study is a retrospective cohort study of all adult patients with BL diagnosed and treated with modern, dose-intense chemotherapeutic regimens from 1998-2008 at two tertiary care institutions. All cases were confirmed by application of WHO 2008 criteria by hematopathologists. Medical records were reviewed for patient-, disease-, and treatment- related factors as well as treatment response and survival. Factors associated with survival were analyzed using Cox proportional hazards modeling. A total of 35 patients were analyzed: 18 patients received rituximab with chemotherapy (R-chemo) and 17 received chemotherapy (chemo) alone. The median age was 42 (range 20-74 years); 57% were male; 71% had Ann Arbor Stage IV disease; 33% had central nervous system involvement; 78% had an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1. R-chemo was associated with significantly longer overall survival (OS) than chemo alone (5-year OS 70% and 29%, respectively, p = 0.040). On multivariate regression analysis, poor performance status and central nervous system involvement were associated with poorer survival. The addition of rituximab to chemotherapy was associated with improved OS in patients with Burkitt lymphoma. Poor performance status and central nervous system involvement were prognostically significant on multivariate analysis.

Development of DOTA-Rituximab to be Labeled with 90Y for Radioimmunotherapy of B-cell Non-Hodgkin Lymphoma

Science.gov (United States)

Johari doha, Fariba; Rahmani, Siyavash; Rikhtechi, Pedram; Rasaneh, Samira; Sheikholislam, Zahra; Shahhosseini, Soraya

2017-01-01

NHL is the most common hematologic cancer in adults. Rituximab is the FDA approved treatment of relapsed or refractory low grade B-cell Non-Hodgkin Lymphoma (NHL). But patients eventually become resistant to rituximab. Since lymphocytes and lymphoma cells are highly radiosensitive, low grade NHL that has relapsed or refractory to standard therapy is treated by RIT in which a beta-emitting radionuclide coupled to anti-CD20 antibody. The association of beta emitter radionuclide to rituximab enhances its therapeutic efficacy. The cells which lack antigen or cells which cannot be reached due to poor vascularization and intratumoral pressure in a bulky tumor would be irradiated and killed by cross fire effect of beta emitter. 90Y, a pure high energy β-emitter with a half-life of 64 h, a maximum energy of 2.28 MeV, and maximum board of 11.3 mm in tissue is radionuclide of choice for radioimmunotherapy of outpatient administration. In this study, rituximab was conjugated to DOTA and radiolabeled with 90YCl3. The stability, affinity, and immunoreactivity of radiolabeled antibody was determined in vitro and the conditions were optimized. Biodistribution studies were done in normal mice. The optimum conditions of conjugation and radiolabeling was 1-2 h at 37 °C and 1 h at 45 °C, respectively. Results showed approximately 4 DOTA molecules conjugated per antibody molecule. The purified antibody was stable and intact over 6 months stored at -20 °C. The result of immunoreactivity (≈70%), affinity (≈3 nM) and biodistribution in normal mice are acceptable. PMID:28979315

Ofatumumab Versus Rituximab Salvage Chemoimmunotherapy in Relapsed or Refractory Diffuse Large B-Cell Lymphoma

DEFF Research Database (Denmark)

van Imhoff, Gustaaf W; McMillan, Andrew; Matasar, Matthew J

2017-01-01

Purpose We compared the efficacy of ofatumumab (O) versus rituximab (R) in combination with cisplatin, cytarabine, and dexamethasone (DHAP) salvage treatment, followed by autologous stem-cell transplantation (ASCT) in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL). Pat...

High treatment efficacy by dual targeting of Burkitt's lymphoma xenografted mice with a {sup 177}Lu-based CD22-specific radioimmunoconjugate and rituximab

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Weber, Tobias; Boetticher, Benedikt; Keller, Armin; Schlegelmilch, Anne; Jaeger, Dirk; Krauss, Juergen [Heidelberg University Hospital, Department of Medical Oncology, National Center for Tumor Diseases, Heidelberg (Germany); Mier, Walter; Kraemer, Susanne; Leotta, Karin [Heidelberg University Hospital, Department of Nuclear Medicine, Heidelberg (Germany); Sauter, Max; Haberkorn, Uwe [Heidelberg University Hospital, Department of Nuclear Medicine, Heidelberg (Germany); German Cancer Research Center (DKFZ), Clinical Cooperation Unit Nuclear Medicine, Heidelberg (Germany); Grosse-Hovest, Ludger [University of Tuebingen, Department of Immunology, Tuebingen (Germany); Arndt, Michaela A.E. [Heidelberg University Hospital, Department of Medical Oncology, National Center for Tumor Diseases, Heidelberg (Germany); German Cancer Research Center (DKFZ), Immunotherapy Program, National Center for Tumor Diseases, Heidelberg (Germany)

2016-03-15

Dual-targeted therapy has been shown to be a promising treatment option in recurrent and/or refractory B-cell non-Hodgkin's lymphoma (B-NHL). We generated radioimmunoconjugates (RICs) comprising either a novel humanized anti-CD22 monoclonal antibody, huRFB4, or rituximab, and the low-energy β-emitter {sup 177}Lu. Both RICs were evaluated as single agents in a human Burkitt's lymphoma xenograft mouse model. To increase the therapeutic efficacy of the anti-CD22 RIC, combination therapy with unlabelled anti-CD20 rituximab was explored. The binding activity of CHX-A''-DTPA-conjugated antibodies to target cells was analysed by flow cytometry. To assess tumour targeting of {sup 177}Lu-labelled antibodies, in vivo biodistribution experiments were performed. For radioimmunotherapy (RIT) studies, non-obese diabetic recombination activating gene-1 (NOD-Rag1{sup null}) interleukin-2 receptor common gamma chain (IL2r γ {sup null}) null mice (NRG mice) were xenografted subcutaneously with Raji Burkitt's lymphoma cells. {sup 177}Lu-conjugated antibodies were administered at a single dose of 9.5 MBq per mouse. For dual-targeted therapy, rituximab was injected at weekly intervals (0.5 - 1.0 mg). Tumour accumulation of RICs was monitored by planar scintigraphy. Conjugation of CHX-A''-DTPA resulted in highly stable RICs with excellent antigen-binding properties. Biodistribution experiments revealed higher tumour uptake of the {sup 177}Lu-labelled anti-CD22 IgG than of {sup 177}Lu-labelled rituximab. Treatment with {sup 177}Lu-conjugated huRFB4 resulted in increased tumour growth inhibition and significantly longer survival than treatment with {sup 177}Lu-conjugated rituximab. The therapeutic efficacy of the anti-CD22 RIC could be markedly enhanced by combination with unlabelled rituximab. These findings suggest that dual targeting with {sup 177}Lu-based CD22-specific RIT in combination with rituximab is a promising new treatment option for

Persistence and selection of an expanded B-cell clone in the setting of rituximab therapy for Sjögren’s syndrome

Science.gov (United States)

2014-01-01

Introduction Subjects with primary Sjögren’s syndrome (SjS) have an increased risk of developing B-cell lymphoma and may harbor monoclonal B-cell expansions in the peripheral blood. Expanded B-cell clones could be pathogenic, and their persistence could exacerbate disease or predispose toward the development of lymphoma. Therapy with anti-CD20 (rituximab) has the potential to eliminate expanded B-cell clones and thereby potentially ameliorate disease. This study was undertaken to identify and track expanded B-cell clones in the blood of subjects with primary SjS who were treated with rituximab. Methods To determine whether circulating B-cell clones in subjects with primary SjS emerge or remain after B cell-depleting therapy with rituximab, we studied the antibody heavy-chain repertoire. We performed single-memory B-cell and plasmablast sorting and antibody heavy-chain sequencing in six rituximab-treated SjS subjects over the course of a 1-year follow-up period. Results Expanded B-cell clones were identified in four out of the six rituximab-treated SjS subjects, based upon the independent amplification of sequences with identical or highly similar VH, DH, and JH gene segments. We identified one SjS subject with a large expanded B-cell clone that was present prior to therapy and persisted after therapy. Somatic mutations in the clone were numerous but did not increase in frequency over the course of the 1-year follow-up, suggesting that the clone had been present for a long period of time. Intriguingly, a majority of the somatic mutations in the clone were silent, suggesting that the clone was under chronic negative selection. Conclusions For some subjects with primary SjS, these data show that (a) expanded B-cell clones are readily identified in the peripheral blood, (b) some clones are not eliminated by rituximab, and (c) persistent clones may be under chronic negative selection or may not be antigen-driven. The analysis of sequence variation among members of an

Radiolabeling parameters of {sup 177}Lu-DOTA-RITUXIMAB

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Massicano, Adriana V.F.; Alcarde, Lais F.; Oliveira, Ricardo S.; Mengatti, Jair; Araujo, Elaine B. de, E-mail: adriana.avfernandes@gmail.com [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil)

2013-07-01

Cancer treatment using radioimmunotherapy (RIT) has been the focus of much research in the last two decades. In RIT, a radioisotope is coupled to a monoclonal antibody (mAb) to form a tumor-specific target agent to improve the cytocidal effect of the mAbs. RIT allows the systemic delivery of radiation to disease target by mAbs while sparing normal tissues. Rituximab® (Mabthera - Roche) is a chimeric mouse-human monoclonal antibody; it selectively binds with high affinity to the CD20 antigen, a hydrophobic transmembrane protein, which is expressed on B-lymphocytes and in more than 90% of B cell non-Hodgkin's lymphomas (NHL). The conjugation and radiolabeling process involve special conditions of pH and temperature, long processes of manipulation and mixing. All this process can damage the antibody structure and compromise its clinical application. Therefore, these parameters must be largely studied. The aim of this work was to evaluate the best radiolabeling conditions of DOTA-rituximab. Briefly, 10 mg of antibody previously purified by ultrafiltration device was conjugated with DOTA-NHS-ester (Macrocyclics) in 50 fold molar excess. The reaction was conducted for 1 hour in phosphate buffer pH 8.0 and gently mixing at room temperature, remaining for 24 hours under refrigeration. The immunoconjugated was purified by size exclusion column and ultrafiltration device. The radiolabeled parameters studied were: immunoconjugated mass, activity of {sup 177}LuCl{sub 3}, reaction time, temperature and pH. The radiochemical purity of the preparations was determined using analysis by thin layer chromatography (TLC-SG plates). The best studied condition presented radiochemical purity above 95% and the integrity of antibody was preserved. (author)

Impact on Medical Cost, Cumulative Survival, and Cost-Effectiveness of Adding Rituximab to First-Line Chemotherapy for Follicular Lymphoma in Elderly Patients: An Observational Cohort Study Based on SEER-Medicare

International Nuclear Information System (INIS)

Griffiths, R. I.; Gleeson, M. L.; Danese, M. D.; Griffiths, R. I.; Mikhael, J.

2012-01-01

Rituximab improves survival in follicular lymphoma (FL), but is considerably more expensive than conventional chemotherapy. We estimated the total direct medical costs, cumulative survival, and cost-effectiveness of adding rituximab to first-line chemotherapy for FL, based on a single source of data representing routine practice in the elderly. Using surveillance, epidemiology, and end results (SEER) registry data plus Medicare claims, we identified 1,117 FL patients who received first-line CHOP (cyclophosphamide (C), doxorubicin, vincristine (V), and prednisone (P)) or CVP +/− rituximab. Multivariate regression was used to estimate adjusted cumulative cost and survival differences between the two groups over four years after beginning treatment. The median age was 73 years (minimum 66 years), 56% had stage III-IV disease, and 67% received rituximab. Adding rituximab to first-line chemotherapy was associated with higher adjusted incremental total cost ($18,695; 95% Confidence Interval (CI) $9,302-$28,643) and longer adjusted cumulative survival (0.18 years; 95% CI 0.10-0.27) over four years of followup. The expected cost-effectiveness was $102,142 (95% CI $34,531-296,337) per life-year gained. In routine clinical practice, adding rituximab to first-line chemotherapy for elderly patients with FL results in higher direct medical costs to Medicare and longer cumulative survival after four years.

International standards for monoclonal antibodies to support pre- and post-marketing product consistency: Evaluation of a candidate international standard for the bioactivities of rituximab.

Science.gov (United States)

Prior, Sandra; Hufton, Simon E; Fox, Bernard; Dougall, Thomas; Rigsby, Peter; Bristow, Adrian

2018-01-01

The intrinsic complexity and heterogeneity of therapeutic monoclonal antibodies is built into the biosimilarity paradigm where critical quality attributes are controlled in exhaustive comparability studies with the reference medicinal product. The long-term success of biosimilars will depend on reassuring healthcare professionals and patients of consistent product quality, safety and efficacy. With this aim, the World Health Organization has endorsed the need for public bioactivity standards for therapeutic monoclonal antibodies in support of current controls. We have developed a candidate international potency standard for rituximab that was evaluated in a multi-center collaborative study using participants' own qualified Fc-effector function and cell-based binding bioassays. Dose-response curve model parameters were shown to reflect similar behavior amongst rituximab preparations, albeit with some differences in potency. In the absence of a common reference standard, potency estimates were in poor agreement amongst laboratories, but the use of the candidate preparation significantly reduced this variability. Our results suggest that the candidate rituximab standard can support bioassay performance and improve data harmonization, which when implemented will promote consistency of rituximab products over their life-cycles. This data provides the first scientific evidence that a classical standardization exercise allowing traceability of bioassay data to an international standard is also applicable to rituximab. However, we submit that this new type of international standard needs to be used appropriately and its role not to be mistaken with that of the reference medicinal product.

Radiolabeling of rituximab with {sup 188}Re and {sup 99m}Tc using the tricarbonyl technology

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Dias, Carla Roberta [Instituto de Pesquisas Energeticas e Nucleares, Av. Professor Lineu Prestes 2242, 05508-000 Sao Paulo (Brazil); Jeger, Simone [Center for Radiopharmaceutical Sciences ETH-PSI-USZ, Paul Scherrer Institute, 5232 Villigen-PSI (Switzerland); Osso, Joao Alberto [Instituto de Pesquisas Energeticas e Nucleares, Av. Professor Lineu Prestes 2242, 05508-000 Sao Paulo (Brazil); Mueller, Cristina; De Pasquale, Christine; Hohn, Alexander; Waibel, Robert [Center for Radiopharmaceutical Sciences ETH-PSI-USZ, Paul Scherrer Institute, 5232 Villigen-PSI (Switzerland); Schibli, Roger, E-mail: roger.schibli@psi.c [Center for Radiopharmaceutical Sciences ETH-PSI-USZ, Paul Scherrer Institute, 5232 Villigen-PSI (Switzerland); Department of Chemistry and Applied Biosciences of the ETH, 8093 Zurich (Switzerland)

2011-01-15

Introduction: The most successful clinical studies of immunotherapy in patients with non-Hodgkin's lymphoma (NHL) use the antibody rituximab (RTX) targeting CD20{sup +} B-cell tumors. Rituximab radiolabeled with {beta}{sup -} emitters could potentiate the therapeutic efficacy of the antibody by virtue of the particle radiation. Here, we report on a direct radiolabeling approach of rituximab with the {sup 99m}Tc- and {sup 188}Re-tricarbonyl core (IsoLink technology). Methods: The native format of the antibody (RTX{sub wt}) as well as a reduced form (RTX{sub red}) was labeled with {sup 99m}Tc/{sup 188}Re(CO){sub 3}. The partial reduction of the disulfide bonds to produce free sulfhydryl groups (-SH) was achieved with 2-mercaptoethanol. Radiolabeling efficiency, in vitro human plasma stability as well as transchelation toward cysteine and histidine was investigated. The immunoreactivity and binding affinity were determined on Ramos and/or Raji cells expressing CD20. Biodistribution was performed in mice bearing subcutaneous Ramos lymphoma xenografts. Results: The radiolabeling efficiency and kinetics of RTX{sub red} were superior to that of RTX{sub wt} ({sup 99m}Tc: 98% after 3 h for RTX{sub red} vs. 70% after 24 h for RTX{sub wt}). {sup 99m}Tc(CO){sub 3}-RTX{sub red} was used without purification for in vitro and in vivo studies whereas {sup 188}Re(CO){sub 3}-RTX{sub red} was purified to eliminate free {sup 188}Re-precursor. Both radioimmunoconjugates were stable in human plasma for 24 h at 37{sup o}C. In contrast, displacement experiments with excess cysteine/histidine showed significant transchelation in the case of {sup 99m}Tc(CO){sub 3}-RTX{sub red} but not with pre-purified {sup 188}Re(CO){sub 3}-RTX{sub red}. Both conjugates revealed high binding affinity to the CD20 antigen (K{sub d}=5-6 nM). Tumor uptake of {sup 188}Re(CO){sub 3}-RTX{sub red} was 2.5 %ID/g and 0.8 %ID/g for {sup 99m}Tc(CO){sub 3}-RTX{sub red} 48 h after injection. The values for other

Splenectomy vs. rituximab as a second-line therapy in immune thrombocytopenic purpura: a single center experience.

Science.gov (United States)

Al Askar, Ahmed S; Shaheen, Naila A; Al Zahrani, Mohsen; Al Otaibi, Mohammed G; Al Qahtani, Bader S; Ahmed, Faris; Al Zughaibi, Mohand; Kamran, Ismat; Mendoza, May Anne; Khan, Altaf

2018-01-01

Immune thrombocytopenic purpura (ITP) is a common hematological disease treated primarily by corticosteroids. The aim of the present study was to compare response rate between patients, underwent splenectomy vs. rituximab as second-line therapy. Adult patients diagnosed with ITP who did not respond to corticosteroids or relapsed during the period 1990-2014 were included in a quasi-experimental study. Categorical variables were compared using Fisher exact test. Response to treatment was compared using logistic regression. Data were analyzed using SAS V9.2. One-hundred and forty-three patients with ITP were identified through medical records. Of 62 patients treated, 30 (48.38%) required second-line therapy. 19 (63%) patients received rituximab, and 11 (37%) underwent splenectomy. Platelets at diagnosis were not different between study groups (p = 0.062). Splenectomy group patients were younger (p = 0.011). Response to second-line therapy showed no significant difference between two groups (OR 2.03, 95% CI (0.21-22.09), p = 0.549). Results did not show a statistically significant difference in platelet counts over time between treatment groups (p = 0.101). When used exclusively as a second-line therapy for steroid-refractory ITP, the response rate was not statistically different between rituximab and splenectomy. However, further large studies are needed to assess the response rates for these treatment modalities as a second-line therapy.

Effects of hypertonic buffer composition on lymph node uptake and bioavailability of rituximab, after subcutaneous administration.

Science.gov (United States)

Fathallah, Anas M; Turner, Michael R; Mager, Donald E; Balu-Iyer, Sathy V

2015-03-01

The subcutaneous administration of biologics is highly desirable; however, incomplete bioavailability after s.c. administration remains a major challenge. In this work we investigated the effects of excipient dependent hyperosmolarity on lymphatic uptake and plasma exposure of rituximab as a model protein. Using Swiss Webster (SW) mice as the animal model, we compared the effects of NaCl, mannitol and O-phospho-L-serine (OPLS) on the plasma concentration of rituximab over 5 days after s.c. administration. An increase was observed in plasma concentrations in animals administered rituximab in hypertonic buffer solutions, compared with isotonic buffer. Bioavailability, as estimated by our pharmacokinetic model, increased from 29% in isotonic buffer to 54% in hypertonic buffer containing NaCl, to almost complete bioavailability in hypertonic buffers containing high dose OPLS or mannitol. This improvement in plasma exposure is due to the improved lymphatic trafficking as evident from the increase in the fraction of dose trafficked through the lymph nodes in the presence of hypertonic buffers. The fraction of the dose trafficked through the lymphatics, as estimated by the model, increased from 0.05% in isotonic buffer to 13% in hypertonic buffer containing NaCl to about 30% for hypertonic buffers containing high dose OPLS and mannitol. The data suggest that hypertonic solutions may be a viable option for improving s.c. bioavailability. Copyright © 2014 John Wiley & Sons, Ltd.

Treatment of post-transplantation lymphoproliferative disorders after kidney transplant with rituximab and conversion to m-TOR inhibitor.

Science.gov (United States)

Nieto-Rios, John Fredy; Gómez de Los Ríos, Sandra Milena; Serna-Higuita, Lina María; Ocampo-Kohn, Catalina; Aristizabal-Alzate, Arbey; Gálvez-Cárdenas, Kenny Mauricio; Zuluaga-Valencia, Gustavo Adolfo

2016-12-30

Post-transplantation lymphoproliferative disorders are serious complications of organ transplantation which treatment is not yet standardized. To describe the clinical response, overall and graft survival of patients in our center with this complication after kidney transplantation, which received rituximab as part of their treatment as well as conversion to m-TOR. Retrospective study, which included patients, diagnosed with post-transplant lymphoproliferative disorders after kidney transplantation from January 2011 to July 2014. Eight cases were found with a wide spectrum of clinical presentations. Most had monomorphic histology, 85% were associated with Epstein-Barr virus, 25% of patients had tumor involvement of the renal graft, and 12.5% ​​had primary central nervous system lymphoma. All patients were managed with reduction of immunosuppression, conversion to m-TOR (except one who lost the graft at diagnosis) and rituximab-based therapy. The overall response rate was 87.5% (62.5% complete response, 25% partial response). Survival was 87.5% with a median follow-up of 34 months. An additional patient lost the graft, with chronic nephropathy already known. All the remaining patients had stable renal function. There are no standardized treatment regimens for lymphoproliferative disorders after kidney transplantation, but these patients can be managed successfully with reduction of immunosuppression, conversion to m-TOR and rituximab-based schemes.

B lymphocyte depletion with the monoclonal antibody rituximab in Graves' disease: a controlled pilot study

DEFF Research Database (Denmark)

El Fassi, Daniel; Nielsen, Claus H; Bonnema, Steen J

2007-01-01

Graves' disease (GD) is a common TSH receptor autoantibody (TRAb)-mediated disorder. Because B lymphocytes are important self-antigen presenting cells and precursors for antibody-secreting plasma cells, temporary B-lymphocyte depletion with the monoclonal antibody rituximab (RTX) might...

Cost-effectiveness of adding rituximab to fludarabine and cyclophosphamide for treatment of chronic lymphocytic leukemia in Ukraine

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Mandrik O

2015-08-01

Full Text Available Olena Mandrik,1 Isaac Corro Ramos,2 Saskia Knies,1,3 Maiwenn Al,1,2 Johan L Severens1,2 1Institute of Health Policy and Management, Erasmus University Rotterdam, Rotterdam, the Netherlands; 2Institute of Medical Technology Assessment (iMTA, Erasmus University Rotterdam, Rotterdam, the Netherlands; 3National Health Care Institute, Diemen, the Netherlands Abstract: The aim of this study was to assess the cost-effectiveness, from a health care perspective, of adding rituximab to fludarabine and cyclophosphamide scheme (FCR versus FC for treatment-naïve and refractory/relapsed Ukrainian patients with chronic lymphocytic leukemia. A decision-analytic Markov cohort model with three health states and 1-month cycle time was developed and run within a life time horizon. Data from two multinational, prospective, open-label Phase 3 studies were used to assess patients' survival. While utilities were generalized from UK data, local resource utilization and disease-associated treatment, hospitalization, and side effect costs were applied. The alternative scenario was performed to assess the impact of lower life expectancy of the general population in Ukraine on the incremental cost-effectiveness ratio (ICER for treatment-naïve patients. One-way, two-way, and probabilistic sensitivity analyses were conducted to assess the robustness of the results. The ICER (in US dollars of treating chronic lymphocytic leukemia patients with FCR versus FC is US$8,704 per quality-adjusted life year gained for treatment-naïve patients and US$11,056 for refractory/relapsed patients. When survival data were modified to the lower life expectancy of the general population in Ukraine, the ICER for treatment-naïve patients was higher than US$13,000. This value is higher than three times the current gross domestic product per capita in Ukraine. Sensitivity analyses have shown a high impact of rituximab costs and a moderate impact of differences in utilities on the ICER

Radioimmunotherapy using {sup 131}I-rituximab in patients with advanced stage B-cell non-Hodgkin's lymphoma: initial experience

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Bienert, Maren; Reisinger, Ingrid; Humplik, Beatrice I.; Reim, Christel; Kroessin, Thomas; Avril, Norbert; Munz, Dieter L. [Charite - Universitaetsmedizin Berlin, Clinic for Nuclear Medicine, Berlin (Germany); Srock, Stefanie; Pezzutto, Antonio [Charite - Universitaetsmedizin Berlin, Department of Haematology and Oncology, Berlin (Germany)

2005-10-01

The aim of this study was to evaluate the safety, toxicity and therapeutic response of non-myeloablative radioimmunotherapy using {sup 131}I-rituximab in previously heavily treated patients with B-cell non-Hodgkin's lymphoma (B-NHL). Nine patients with relapsed, refractory or transformed B-NHL received ten radioimmunotherapies. Patients had a median of 5 (range 2-7) prior standard therapies. Four patients had received prior high-dose chemotherapy followed by autologous stem cell transplantation, and eight had received prior rituximab therapy. Histopathology consisted of four mantle cell, one follicular and four diffuse large B-cell lymphomas. Rituximab, a monoclonal chimeric anti-CD20 antibody (IDEC-C2B8), was labelled with {sup 131}I using the Iodogen method. The administered activity (2,200{+-}600 MBq) was based on a dosimetrically calculated 45 cGy total-body radiation dose. All patients received an infusion of 2.5 mg/kg of rituximab prior to administration of the radiopharmaceutical. No acute adverse effects were observed after the administration of{sup 131}I-rituximab. Radioimmunotherapy was safe in our patient group and achieved one complete response ongoing at 14 months and two partial responses progressing at 12 and 13 months after treatment. One partial responder was re-treated with radioimmunotherapy and achieved an additional progression-free interval of 7 months. Four non-responders with bulky disease died 4.8{+-}2.0 months after therapy. Three patients had an elevated serum lactate dehydrogenase (LDH) level prior to radioimmunotherapy and none of the patients responded. Of two patients who received radioimmunotherapy as an additional treatment after salvage chemotherapy, one continues to be disease-free at 9 months and one relapsed at 5 months' follow-up. Reversible grade 3 or 4 haematological toxicity occurred in seven of nine patients. Median nadirs were 35 days for platelets, 44 days for leucocytes and 57 days for erythrocytes. (orig.)

Activatory and inhibitory Fcγ receptors augment rituximab-mediated internalization of CD20 independent of signaling via the cytoplasmic domain.

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Vaughan, Andrew T; Chan, Claude H T; Klein, Christian; Glennie, Martin J; Beers, Stephen A; Cragg, Mark S

2015-02-27

Type I anti-CD20 mAb such as rituximab and ofatumumab engage with the inhibitory FcγR, FcγRIIb on the surface of B cells, resulting in immunoreceptor tyrosine-based inhibitory motif (ITIM) phosphorylation. Internalization of the CD20·mAb·FcγRIIb complex follows, the rate of which correlates with FcγRIIb expression. In contrast, although type II anti-CD20 mAb such as tositumomab and obinutuzumab also interact with and activate FcγRIIb, this interaction fails to augment the rate of CD20·mAb internalization, raising the question of whether ITIM phosphorylation plays any role in this process. We have assessed the molecular requirements for the internalization process and demonstrate that in contrast to internalization of IgG immune complexes, FcγRIIb-augmented internalization of rituximab-ligated CD20 occurs independently of the FcγRIIb ITIM, indicating that signaling downstream of FcγRIIb is not required. In transfected cells, activatory FcγRI, FcγRIIa, and FcγRIIIa augmented internalization of rituximab-ligated CD20 in a similar manner. However, FcγRIIa mediated a slower rate of internalization than cells expressing equivalent levels of the highly homologous FcγRIIb. The difference was maintained in cells expressing FcγRIIa and FcγRIIb lacking cytoplasmic domains and in which the transmembrane domains had been exchanged. This difference may be due to increased degradation of FcγRIIa, which traffics to lysosomes independently of rituximab. We conclude that the cytoplasmic domain of FcγR is not required for promoting internalization of rituximab-ligated CD20. Instead, we propose that FcγR provides a structural role in augmenting endocytosis that differs from that employed during the endocytosis of immune complexes. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

Impact on Medical Cost, Cumulative Survival, and Cost-Effectiveness of Adding Rituximab to First-Line Chemotherapy for Follicular Lymphoma in Elderly Patients: An Observational Cohort Study Based on SEER-Medicare

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Robert I. Griffiths

2012-01-01

Full Text Available Rituximab improves survival in follicular lymphoma (FL, but is considerably more expensive than conventional chemotherapy. We estimated the total direct medical costs, cumulative survival, and cost-effectiveness of adding rituximab to first-line chemotherapy for FL, based on a single source of data representing routine practice in the elderly. Using surveillance, epidemiology, and end results (SEER registry data plus Medicare claims, we identified 1,117 FL patients who received first-line CHOP (cyclophosphamide (C, doxorubicin, vincristine (V, and prednisone (P or CVP +/− rituximab. Multivariate regression was used to estimate adjusted cumulative cost and survival differences between the two groups over four years after beginning treatment. The median age was 73 years (minimum 66 years, 56% had stage III-IV disease, and 67% received rituximab. Adding rituximab to first-line chemotherapy was associated with higher adjusted incremental total cost ($18,695; 95% Confidence Interval (CI $9,302–$28,643 and longer adjusted cumulative survival (0.18 years; 95% CI 0.10–0.27 over four years of followup. The expected cost-effectiveness was $102,142 (95% CI $34,531–296,337 per life-year gained. In routine clinical practice, adding rituximab to first-line chemotherapy for elderly patients with FL results in higher direct medical costs to Medicare and longer cumulative survival after four years.

Results of a multicenter prospective clinical study in Japan for evaluating efficacy and safety of desensitization protocol based on rituximab in ABO-incompatible kidney transplantation.

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Takahashi, Kota; Saito, Kazuhide; Takahara, Shiro; Fuchinoue, Shohei; Yagisawa, Takashi; Aikawa, Atsushi; Watarai, Yoshihiko; Yoshimura, Norio; Tanabe, Kazunari; Morozumi, Kunio; Shimazu, Motohide

2017-08-01

Deceased organ donations are rare in Japan, with most kidney transplants performed from a limited number of living donors. Researchers have thus developed highly successful ABO-incompatible transplantation procedures, emphasizing preoperative desensitization and postoperative immunosuppression. A recent open-label, single-arm, multicenter clinical study prospectively examined the efficacy and safety of rituximab/mycophenolate mofetil desensitization in ABO-incompatible kidney transplantation without splenectomy. Mycophenolate mofetil and low dose steroid were started 28 days pretransplant, followed by two doses of rituximab 375 mg/m 2 at day -14 and day -1, and postoperative immunosuppression with tacrolimus or ciclosporin and basiliximab. The primary endpoint was the non-occurrence rate of acute antibody-mediated rejection. Patient survival and graft survival were monitored for 1 year posttransplant. Eighteen patients received rituximab and underwent ABO-incompatible kidney transplantation. CD19-positive peripheral B cell count decreased rapidly after the first rituximab infusion and recovered gradually after week 36. The desensitization protocol was tolerable, and most rituximab-related infusion reactions were mild. No anti-A/B antibody-mediated rejection occurred with this series. One patient developed anti-HLA antibody-mediated rejection (Banff 07 type II) on day 2, which was successfully managed. Patient and graft survival were both 100 % after 1 year. Our desensitization protocol was confirmed to be clinically effective and with acceptable toxicities for ABO-I-KTx (University Hospital Medical Information Network Registration Number: UMIN000006635).

An update on the evidence for the efficacy and safety of rituximab in the management of neuromyelitis optica

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Collongues, Nicolas; de Seze, Jérôme

2016-01-01

Neuromyelitis optica spectrum disorders (NMOSDs) is a new concept which includes classical neuromyelitis optica (NMO) and partial forms of NMO such as recurrent optic neuritis with positive aquaporin-4 antibodies (AQP4) or brainstem symptoms (intractable hiccups or vomiting). This disease is clearly distinguished from multiple sclerosis (MS) and the therapeutic approach is clearly different. Rituximab is actually considered to be one of the most efficient treatments of NMOSD, even if class I studies are clearly lacking. In the present review, we describe the state of the art about rituximab treatment in NMOSD, including adults and children, plus its efficacy and tolerance and we also underline the questions that should be addressed in the near future. PMID:27134673

An update on the evidence for the efficacy and safety of rituximab in the management of neuromyelitis optica.

Science.gov (United States)

Collongues, Nicolas; de Seze, Jérôme

2016-05-01

Neuromyelitis optica spectrum disorders (NMOSDs) is a new concept which includes classical neuromyelitis optica (NMO) and partial forms of NMO such as recurrent optic neuritis with positive aquaporin-4 antibodies (AQP4) or brainstem symptoms (intractable hiccups or vomiting). This disease is clearly distinguished from multiple sclerosis (MS) and the therapeutic approach is clearly different. Rituximab is actually considered to be one of the most efficient treatments of NMOSD, even if class I studies are clearly lacking. In the present review, we describe the state of the art about rituximab treatment in NMOSD, including adults and children, plus its efficacy and tolerance and we also underline the questions that should be addressed in the near future.

USE OF RITUXIMAB IN AUTOIMMUNE DISEASES: NEW ASPECTS

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Dmitry Evgenyevich Karateyev

2010-01-01

Full Text Available It has been noted that off-label indication for Rituximab (RTX in rheumatological care indubitably requires its confirmation in the randomized clinical trials. A particular cautious approach should be taken in extending the indications for therapy with gene-engineering biologicals because of the intricacy and interaction of different immunoregulatory mechanisms. Nonetheless, it is stated that much clinical experience with RTX used in most severely ill therapy-resistant patients may serve as a basis for its prescription in a number of most complex inflammatory rheumatic diseases (RDs. There is new evidence for the use of RTX in various RDs differing in their clinical picture, course, and pathogenesis, such as spondyloarthritis, systemic lupus erythematosus, systemic vasculitis.

Nye behandlinger af Graves' sygdom med fokus på det B-lymfocyt-depleterende antistof rituximab

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Nielsen, Claus Henrik; El Fassi, Daniel; Hegedüs, Laszlo

2008-01-01

Graves' disease (GD) is caused by autoantibodies to the thyrotropin receptor (TRAb). In a controlled study using the B-lymphocyte depleting agent rituximab (RTX), an RTX-specific effect was found on long-term remission following methimazole (MMI) therapy. However, benefits were limited to patients...

Preparation and radiolabeling of a lyophilized (kit) formulation of DOTA-rituximab with ⁹⁰Y and ¹¹¹In for domestic radioimmunotherapy and radioscintigraphy of non-Hodgkin's lymphoma.

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Gholipour, Nazila; Jalilian, Amir Reza; Khalaj, Ali; Johari-Daha, Fariba; Yavari, Kamal; Sabzevari, Omid; Khanchi, Ali Reza; Akhlaghi, Mehdi

2014-07-29

On the basis of results of our previous investigations on 90Y-DTPA-rituximab and in order to fulfil national demands to radioimmunoconjugates for radioscintigraphy and radioimmunotherapy of Non-Hodgkin's Lymphoma (NHL), preparation and radiolabeling of a lyophilized formulation (kit) of DOTA-rituximab with 111In and 90Y was investigated. 111In and 90Y with high radiochemical and radionuclide purity were prepared by 112Cd (p,2n)111In nuclear reaction and a locally developed 90Sr/90Y generator, respectively. DOTA-rituximab immunoconjugates were prepared by the reaction of solutions of p-SCN-Bz-DOTA and rituximab in carbonate buffer (pH = 9.5) and the number of DOTA per molecule of conjugates were determined by transchelation reaction between DOTA and arsenaso yttrium(III) complex. DOTA-rituximab immunoconjugates were labeled with 111In and 90Y and radioimmunoconjugates were checked for radiochemical purity by chromatography methods and for immunoreactivity by cell-binding assay using Raji cell line. The stability of radiolabeled conjugate with the approximate number of 7 DOTA molecules per one rituximab molecule which was prepared in moderate yield and showed moderate immunoreactivity, compared to two other prepared radioimmunoconjugates, was determined at different time intervals and against EDTA and human serum by chromatography methods and reducing SDS-polyacrylamide gel electrophoresis, respectively. The biodistribution of the selected radioimmunoconjugate in rats was determined by measurement of the radioactivity of different organs after sacrificing the animals by ether asphyxiation. The radioimmunoconjugate with approximate DOTA/rituximab molar ratio of 7 showed stability after 24 h at room temperature, after 96 h at 4°C, as the lyophilized formulation after six months storage and against EDTA and human serum. This radioimmunoconjugate had a biodistribution profile similar to that of 90Y-ibritumomab, which is approved by FDA for radioimmunotherapy of NHL

Rituximab Treatment Prevents Lymphoma Onset in Gastric Cancer Patient-Derived Xenografts

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Simona Corso

2018-05-01

Full Text Available Patient-Derived Xenografts (PDXs, entailing implantation of cancer specimens in immunocompromised mice, are emerging as a valuable translational model that could help validate biologically relevant targets and assist the clinical development of novel therapeutic strategies for gastric cancer.More than 30% of PDXs generated from gastric carcinoma samples developed human B-cell lymphomas instead of gastric cancer. These lymphomas were monoclonal, Epstein Barr Virus (EBV positive, originated tumorigenic cell cultures and displayed a mutational burden and an expression profile distinct from gastric adenocarcinomas. The ability of grafted samples to develop lymphomas did not correlate with patient outcome, nor with the histotype, the lymphocyte infiltration level, or the EBV status of the original gastric tumor, impeding from foreseeing lymphoma onset. Interestingly, lymphoma development was significantly more frequent when primary rather than metastatic samples were grafted.Notably, the development of such lympho-proliferative disease could be prevented by a short rituximab treatment upon mice implant, without negatively affecting gastric carcinoma engraftment.Due to the high frequency of human lymphoma onset, our data show that a careful histologic analysis is mandatory when generating gastric cancer PDXs. Such care would avoid misleading results that could occur if testing of putative gastric cancer therapies is performed in lymphoma PDXs. We propose rituximab treatment of mice to prevent lymphoma development in PDX models, averting the loss of human-derived samples.

Superior efficacy of rituximab-based chemoimmunotherapy as an initial therapy in newly diagnosed patients with B cell indolent lymphomas: long-term results from a single center in China

International Nuclear Information System (INIS)

Li, Zengjun; Li, Fei; Yi, Shuhua; Gu, Zhimin; Yu, Zhen; Xu, Yan; Feng, Xiaoyan; Liu, Wei; Zou, Dehui; Qi, Junyuan; Zhan, Fenghuang; Qiu, Lugui

2015-01-01

Rituximab has been confirmed to improve the survival of patients with B cell indolent non-Hodgkin lymphomas (B-iNHLs) in Western world as previously reported, however, it is rarely reported in Chinese cohort. This study is to investigate the efficacy and safety of rituximab-based chemoimmunotherapy and select subpopulations most sensitive to the regimen in Chinese B-iNHL patients. 334 B-iNHL patients from our center were retrospectively assessed. Patients received R-based chemoimmunotherapy showed significantly higher rates of overall response (OR) (93.0 % vs. 53.4 %, P < 0.001) and complete response (CR) (63.3 % vs. 16.0 %, P < 0.001) compared with the patients received other therapies. Survival analysis showed that rituximab-based chemoimmunotherapy could obviously improve the progression-free survival (PFS) (110 vs. 49 months, P = 0.001) and overall survival (OS) (120 vs. 72 months, P < 0.001) in patients with B-iNHLs. Interestingly, in chronic lymphocytic leukemia (CLL) patients, we found that the patients with β2-microglobulin (β2-MG) < 3.5 mg/L, lactate dehydrogenase (LDH) < 220 U/L, zeta-chain-associated protein kinase 70 (ZAP-70) negative, and non high-risk genetic abnormality could achieve more benefits from R-based regimens with higher CR rate (P = 0.003, 0.029, 0.013 and 0.038, respectively). Meanwhile, more CLL patients achieved minimal residual disease (MRD) negative after rituximab-based treatment (46.5 % vs. 10.3 %, P < 0.001). Moreover, CLL patients with MRD < 1 %, LDH < 220 U/L, complete remission (CR) or partial remission (PR), β2-MG < 3.5 mg/L and non high-risk cytogenetic abnormality showed superior outcome compared to the controls (P = 0.001, 0.000, 0.000, 0.001 and 0.013, respectively). No other side-effects increased in chemoimmunotherapy group except the elevation of grade 3–4 neutropenia. Our results demonstrate the superior efficacy of rituximab–based chemoimmunotherapy as an initial therapy in Chinese cohort with newly diagnosed B

Efficacy of Rituximab in Refractory Inflammatory Myopathies Associated with Anti- Synthetase Auto-Antibodies: An Open-Label, Phase II Trial.

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Yves Allenbach

Full Text Available Anti-synthetase syndrome (anti-SS is frequently associated with myositis and interstitial lung disease (ILD. We evaluated prospectively, in a multicenter, open-label, phase II study, the efficacy of rituximab on muscle and lung outcomes.Patients were enrolled if they were refractory to conventional treatments (prednisone and at least 2 immunosuppressants. They received 1 g of rituximab at D0, D15, and M6. The primary endpoint was muscular improvement based on manual muscular testing (MMT10, Kendall score in 10 muscles at M12. Secondary endpoints were normalization of creatine kinase (CK level, ILD improvement based on forced vital capacity and/or diffuse capacity for carbon monoxide, and number and/or doses of associated immunosuppressants.Twelve patients were enrolled, and 10 completed the study. Only 2 patients presented an improvement of at least 4 points on at least two muscle groups (primary end-point. Overall, seven patients had an increase of at least 4 points on MMT10. CK level decreased from 399 IU/L (range, 48-11,718 to 74.5 IU/L (range, 40-47,857. Corticosteroid doses decreased from 52.5 mg/d (range, 10-70 to 9 mg/d (range, 7-65 and six patients had a decrease in the burden of their associated immunosuppressants. At baseline, all 10 patients presented with ILD. At M12, improvement of ILD was observed in 5 out of the 10 patients, stabilization in 4, and worsening in 1.This pilot study of rituximab treatment in patients with refractory anti-SS provided data on evolution of muscular and pulmonary parameters. Rituximab should now be evaluated in a larger, controlled study for this homogenous group of patients.Clinicaltrials.gov NCT00774462.

Severe neuropsychiatric systemic lupus erythematosus successfully treated with rituximab: an alternative to standard of care

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Chessa E

2017-09-01

Full Text Available Elisabetta Chessa, Matteo Piga, Alberto Floris, Alessandro Mathieu, Alberto Cauli Rheumatology Unit, University Clinic AOU of Cagliari, Cagliari, Italy Abstract: Demyelinating syndrome secondary to systemic lupus erythematosus (DS-SLE is a rare encephalomyelitis burden with a high risk of disability and death. We report on a 49-year-old Caucasian woman with systemic lupus erythematosus (SLE complicated by severe cognitive dysfunction, brainstem disease, cranial nerve palsies, weakness and numbness in limbs and multiple discrete magnetic resonance imaging (MRI areas of damage within the white matter of semioval centers, temporal lobe, external capsule, claustrum, subinsular regions and midbrain. She also had multiple mononeuritis diagnosed through sensory and motor nerve conduction study. She was diagnosed with severe DS-SLE prominently involving the brain and was treated with 500 mg methylprednisolone (PRE pulses for 3 consecutive days, followed by one single pulse of 500 mg cyclophosphamide, and 1 g rituximab, which was then repeated 14 days later. PRE 25 mg/day, rapidly tapered to 7.5 mg/day in 6 months, and mycophenolate mofetil 1 g/day were prescribed as maintenance therapy. She had progressive and sustained improvement in neurological symptoms with almost complete resolution of brain MRI lesions after 1 year. B-cell depleting therapy could be considered as a possible alternative to standard of care in the management of severe inflammatory neuropsychiatric SLE but it should be associated with a conventional immunosuppressant as maintenance treatment to reduce the risk of flare and reduce corticosteroids dose. Keywords: systemic lupus erythematosus, neuropsychiatric lupus, rituximab, demyelinating syndrome, brain MRI

Off-label use of rituximab for systemic lupus erythematosus in Europe

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Ryden-Aulin, Monica; Boumpas, Dimitrios T; Bultink, Irene

2016-01-01

Objectives: Rituximab (RTX) is a biological treatment used off-label in patients with systemic lupus erythematosus (SLE). This survey aimed to investigate the off-label use of RTX in Europe and compare the characteristics of patients receiving RTX with those receiving conventional therapy. Methods...... organ manifestations for which either RTX or conventional therapy was initiated were lupus nephritis followed by musculoskeletal and haematological. The reason for treatment was, besides disease control, corticosteroid-sparing for patients treated with conventional therapy. Conclusions: RTX use for SLE...

Increased T cell proliferative responses to islet antigens identify clinical responders to anti-CD20 monoclonal antibody (rituximab) therapy in type 1 diabetes.

Science.gov (United States)

Herold, Kevan C; Pescovitz, Mark D; McGee, Paula; Krause-Steinrauf, Heidi; Spain, Lisa M; Bourcier, Kasia; Asare, Adam; Liu, Zhugong; Lachin, John M; Dosch, H Michael

2011-08-15

Type 1 diabetes mellitus is believed to be due to the autoimmune destruction of β-cells by T lymphocytes, but a single course of rituximab, a monoclonal anti-CD20 B lymphocyte Ab, can attenuate C-peptide loss over the first year of disease. The effects of B cell depletion on disease-associated T cell responses have not been studied. We compare changes in lymphocyte subsets, T cell proliferative responses to disease-associated target Ags, and C-peptide levels of participants who did (responders) or did not (nonresponders) show signs of β-cell preservation 1 y after rituximab therapy in a placebo-controlled TrialNet trial. Rituximab decreased B lymphocyte levels after four weekly doses of mAb. T cell proliferative responses to diabetes-associated Ags were present at baseline in 75% of anti-CD20- and 82% of placebo-treated subjects and were not different over time. However, in rituximab-treated subjects with significant C-peptide preservation at 6 mo (58%), the proliferative responses to diabetes-associated total (p = 0.032), islet-specific (p = 0.048), and neuronal autoantigens (p = 0.005) increased over the 12-mo observation period. This relationship was not seen in placebo-treated patients. We conclude that in patients with type 1 diabetes mellitus, anti-B cell mAb causes increased proliferative responses to diabetes Ags and attenuated β-cell loss. The way in which these responses affect the disease course remains unknown.

Treatment of neuromyelitis optica and neuromyelitis optica spectrum disorders with rituximab using a maintenance treatment regimen and close CD19 B cell monitoring. A six-year follow-up.

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Evangelopoulos, M E; Andreadou, E; Koutsis, G; Koutoulidis, V; Anagnostouli, M; Katsika, P; Evangelopoulos, D S; Evdokimidis, I; Kilidireas, C

2017-01-15

Neuromyelitis optinca (NMO) represents a serious demyelinating disease of the central nervous system selectively attacking the spinal cord and optic nerve. Early differential diagnosis from multiple sclerosis is of vital importance, as NMO mandates immunosuppressive and not immunomodulatory treatment. Rituximab has been recently introduced as a treatment option for NMO. However, optimal surrogate measures and treatment intervals are still unclear. Five patients (females, mean age 54±10.21years) with NMO and NMO spectrum disorders (NMOSD) were evaluated with respect to disability and relapse rate. All patients were found positive for NMO IgG. All patients (three with NMO and two with NMOSD, 1 patient with recurrent optic neuritis and 1 patient with recurrent myelitis) had received rituximab treatment for six years. One patient with NMOSD received cyclophosphamide prior to rituximab while two were misdiagnosed as multiple sclerosis and had received interferon treatment. All received rituximab infusion of 375mg/m 2 once per week for 4weeks and then every two months for the first two years and then every six months. B-cell counts were measured every two months and were kept in almost undetectable levels. No relapse was noted during the treatment period while EDSS score was improved in all patients. No severe adverse effects occurred during RTX treatment. Rituximab treatment on NMO and NMOSD patients showed significant improvement in disability and relapse-rate without any significant adverse effects. Copyright © 2016. Published by Elsevier B.V.

Clinical scale preparation and evaluation of {sup 131}I-Rituximab for Non-Hodgkin's lymphoma

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Kameswaran, Mythili; Vimalnath, K. Viswanathan; Rajeswari, Ardhi; Joshi, Prahlad Vasudeo; Samuel, Grace [Bhabha Atomic Research Centre, Mumbai (India). Radiopharmaceuticals Div.; Sarma, H.D. [Bhabha Atomic Research Centre, Mumbai (India). Radiation Biology and Health Sciences Div.

2014-09-01

Radioimmunotherapy (RIT) with anti CD20 MoAb conjugated to a β{sup -} emitting radioisotope like {sup 131}I or {sup 90}Y has the added advantage of delivering radiation not only to tumor cells that bind the antibody but also due to a crossfire effect, to neighboring tumor cells inaccessible to the antibody. In order to make available an indigenous radioimmunotherapeutic agent for Non Hodgkin's Lymphoma (NHL), radioiodinated Rituximab has been prepared and evaluated at a clinical scale. Radioiodination of Rituximab was performed by the conventional Chloramine T method using 7.4 GBq Na{sup 131}I in a lead shielded plant. Six batches of radioiodination were prepared and characterized by electrophoresis and HPLC to evaluate the reproducibility of the product. The product remained stable retaining the radiochemical purity > 95% upto 5 days after radioiodination. In vitro cell binding studies and biodistribution studies in normal Swiss mice have indicated the potential of this molecule as a radioimmunotherapeutic agent for NHL. (orig.)

Ibrutinib plus rituximab for patients with high-risk chronic lymphocytic leukaemia: a single-arm, phase 2 study

Science.gov (United States)

Burger, Jan A.; Keating, Michael J.; Wierda, William G.; Hartmann, Elena; Hoellenriegel, Julia; Rosin, Nathalie Y.; de Weerdt, Iris; Jeyakumar, Ghayathri; Ferrajoli, Alessandra; Cardenas-Turanzas, Marylou; Lerner, Susan; Jorgensen, Jeffrey L; Nogueras-González, Graciela M.; Zacharian, Gracy; Huang, Xuelin; Kantarjian, Hagop; Garg, Naveen; Rosenwald, Andreas; O’Brien, Susan

2014-01-01

Summary Background Ibrutinib, an orally administered covalent inhibitor of Bruton tyrosine kinase (BTK), is an effective therapy for patients with relapsed chronic lymphocytic leukemia (CLL). We investigated the activity and safety of the combination of ibrutinib with the monoclonal antibody rituximab (iR) in patients with high-risk CLL. Methods In this single-arm, phase 2 studywe enrolled 40 patients with high-risk CLL at MD Anderson Cancer Center, Houston, Texas, USA. Patients with symptomatic CLL requiring therapy received 28 day cycles of once-daily ibrutinib 420 mg , together with rituximab (weekly during cycle 1, then once per cycle until cycle 6), followed by continuous single-agent ibrutinib. The primary endpoint was progression-free survival (PFS) in the intention-to-treat population. This study is registered with ClinicalTrials.gov, number NCT01520519 and is no longer accruing patients. Findings Between February 28, 2012 and September 11, 2012, we enrolled 40 CLL patients with high-risk disease features. 20 patients had del17p or TP53 mutations (16 previously treated, 4 untreated), 13 had relapsed CLL with del11q, and 7 patients a PFS infections occurred in 4 patients (10%), no grade 4 or 5 infections occurred. At 18 months, the Kaplan Meier estimate of progression-free survival was 78% (95% CI 60.6–88.5) (del[17p] or TP53 mutation: 72%, 95% CI: 45.6–87.6) Interpretation Ibrutinib in combination with rituximab is a well-tolerated regimen for patients with high-risk CLL. It induces high rates of remissions and has positive impact on QOL in this difficult-to-treat patient population. These encouraging data merit further investigation of the added benefit of rituximab as combination partner for ibrutinib in an ongoing randomized trial, in which single-agent ibrutinib is compared to iR combination therapy (NCT02007044). Funding Pharmacyclics, Inc., Cancer Prevention and Research Institute of Texas (CPRIT), Leukemia & Lymphoma Society, NCI Grant P30 CA

Pre-emptive treatment with rituximab of molecular relapse after autologous stem cell transplantation in mantle cell lymphoma

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Andersen, Niels S; Pedersen, Lone B; Laurell, Anna

2009-01-01

PURPOSE: Minimal residual disease (MRD) is predictive of clinical progression in mantle-cell lymphoma (MCL). According to the Nordic MCL-2 protocol we prospectively analyzed the efficacy of pre-emptive treatment using rituximab to MCL patients in molecular relapse after autologous stem cell...

Positron Emission Tomography of (64)Cu-DOTA-Rituximab in a Transgenic Mouse Model Expressing Human CD20 for Clinical Translation to Image NHL

DEFF Research Database (Denmark)

Natarajan, Arutselvan; Gowrishankar, Gayatri; Nielsen, Carsten Haagen

2012-01-01

PURPOSE: This study aims to evaluate (64)Cu-DOTA-rituximab (PETRIT) in a preclinical transgenic mouse model expressing human CD20 for potential clinical translation. PROCEDURES: (64)Cu was chelated to DOTA-rituximab. Multiple radiolabeling, quality assurance, and imaging experiments were performed....... The human CD20 antigen was expressed in B cells of transgenic mice (CD20TM). The mice groups studied were: (a) control (nude mice, n¿=¿3) that received 7.4 MBq/dose, (b) with pre-dose (CD20TM, n¿=¿6) received 2 mg/kg pre-dose of cold rituximab prior to PETRIT of 7.4 MBq/dose, and (c) without pre-dose (CD20......TM, n¿=¿6) PETRIT alone received 7.4 MBq/dose. Small animal PET was used to image mice at various time points (0, 1, 2, 4, 24, 48, and 72 h). The OLINDA/EXM software was used to determine the human equivalent dose for individual organs. RESULTS: PETRIT was obtained with a specific activity of 545...

Patients with diffuse large B-cell lymphoma of germinal center origin with BCL2 translocations have poor outcome, irrespective of MYC status: a report from an International DLBCL rituximab-CHOP Consortium Program Study.

NARCIS (Netherlands)

Visco, C.; Tzankov, A.; Xu-Monette, Z.Y.; Miranda, R.N.; Tai, Y.C.; Li, Y.; Liu, W.M.; d'Amore, E.S.; Li, Y.O.; Montes-Moreno, S.; Dybkaer, K.; Chiu, A.; Orazi, A.; Zu, Y.; Bhagat, G.; Wang, H.Y.; Dunphy, C.H.; His, E.D.; Zhao, X.F.; Choi, W.W.; Krieken, J.H.J.M. van; Huang, Q.; Ai, W.; O'Neill, S.; Ponzoni, M.; Ferreri, A.J.; Kahl, B.S.; Winter, J.N.; Go, R.S.; Dirnhofer, S.; Piris, M.A.; Moller, M.B.; Wu, L.; Medeiros, L.J.; Young, K.H.

2013-01-01

Diffuse large B-cell lymphoma can be classified by gene expression profiling into germinal center and activated B-cell subtypes with different prognoses after rituximab-CHOP. The importance of previously recognized prognostic markers, such as Bcl-2 protein expression and BCL2 gene abnormalities, has

HDL protein composition alters from proatherogenic into less atherogenic and proinflammatory in rheumatoid arthritis patients responding to rituximab

NARCIS (Netherlands)

Raterman, Hennie G.; Levels, Han; Voskuyl, Alexandre E.; Lems, Willem F.; Dijkmans, Ben A.; Nurmohamed, Michael T.

2013-01-01

An atherogenic lipid profile is an established risk factor for cardiovascular (CV) diseases. Interestingly, high inflammatory states as present in rheumatoid arthritis (RA) are associated with unfavourable lipid profile. Data about effects of novel immunomodulating agents as rituximab (RTX) on lipid

Efficiency of using rituximab in a patient with generalized granulomatosis with polyangiitis: A case report

Directory of Open Access Journals (Sweden)

Gulazyk Malikovna Koilubaeva

2014-01-01

Full Text Available Systemic vasculitides (SVs are characterized by inflammation of the blood vessels wall; the spectrum of their clinical manifestations depends on the type, extent, and location of affected vessels and the activity of systemic inflammation. The etiology of most primary SVs is unknown. Antineutrophil cytoplasmic antibodies (ANCAs are implicated in its pathogenesis. The presence of ANCAa in patients' serum and the correlation of their level with the severity of clinical manifestations served as a basis for identifying a subgroup of systemic necrotizing vasculitides associated with ANCA synthesis: granulomatosis with polyangiitis (GPA, microscopic polyangiitis, and Churg – Strauss syndrome. GPA is characterized by systemic granulomatous necrotizing vasculitis involving the small vessels of the upper respiratory tract, lung, and kidney.The paper describes a case of difficult diagnosis and successful rituximab (RTM treatment of generalized GPA in a 45-year-old female patients. The disease occurred with local damage to the upper respiratory tract, granulomatous inflammation of the pulmonary vessels to form multiple infiltrates with lung tissue destruction elements and necrotizing glomerulonephritis. Despite intensive immunosuppressive treatment, there was a rapid GPA progression with the further development of respiratory failure, which had been induced by stenotic laryngitis subglottica leading to tracheostoma. Damage to the organ of vision could lead to severe complications, including amaurosis. RMT was shown to be effective in treating generalized GPA with a poor prognosis.

Targeted alpha therapy in vivo: direct evidence for single cancer cell kill using 149Tb-rituximab

International Nuclear Information System (INIS)

Beyer, G.J.; Soloviev, D.; Buchegger, F.; Miederer, M.; Vranjes-Duric, S.; Comor, J.J.; Kuenzi, G.; Hartley, O.; Senekowitsch-Schmidtke, R.

2004-01-01

This study demonstrates high-efficiency sterilisation of single cancer cells in a SCID mouse model of leukaemia using rituximab, a monoclonal antibody that targets CD20, labelled with terbium-149, an alpha-emitting radionuclide. Radio-immunotherapy with 5.5 MBq labelled antibody conjugate (1.11 GBq/mg) 2 days after an intravenous graft of 5.10 6 Daudi cells resulted in tumour-free survival for >120 days in 89% of treated animals. In contrast, all control mice (no treatment or treated with 5 or 300 μg unlabelled rituximab) developed lymphoma disease. At the end of the study period, 28.4%±4% of the long-lived daughter activity remained in the body, of which 91.1% was located in bone tissue and 6.3% in the liver. A relatively high daughter radioactivity concentration was found in the spleen (12%±2%/g), suggesting that the killed cancer cells are mainly eliminated through the spleen. This promising preliminary in vivo study suggests that targeted alpha therapy with 149 Tb is worthy of consideration as a new-generation radio-immunotherapeutic approach. (orig.)

Impact of the use of autologous stem cell transplantation at first relapse both in naïve and previously rituximab exposed follicular lymphoma patients treated in the GELA/GOELAMS FL2000 study

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Le Gouill, Steven; De Guibert, Sophie; Planche, Lucie; Brice, Pauline; Dupuis, Jehan; Cartron, Guillaume; Van Hoof, Achiel; Casasnovas, Olivier; Gyan, Emmanuel; Tilly, Hervé; Fruchart, Christophe; Deconinck, Eric; Fitoussi, Olivier; Gastaud, Lauris; Delwail, Vincent; Gabarre, Jean; Gressin, Rémy; Blanc, Michel; Foussard, Charles; Salles, Gilles

2011-01-01

Background We analyzed detailed characteristics and salvage treatment in 175 follicular lymphoma patients from the FL2000 study who were in progression after first-line therapy with or without addition of rituximab to chemotherapy and interferon. Design and Methods The impact of using autologous stem cell transplantation and/or rituximab administration at first progression was investigated, taking into account initial therapy. With a median follow up of 31 months, 3-year event free and overall survival rates after progression were 50% (95%CI 42–58%) and 72% (95%CI 64–78%), respectively. Results The 3-year event free rate of rituximab re-treated patients (n=112) was 52% (95%CI 41–62%) versus 40% (95%CI 24–55%) for those not receiving rituximab second line (n=53) (P=0.075). There was a significant difference in 3-year overall survival between patients receiving autologous stem cell transplantation and those not: 92% (95%CI 78–97%) versus 63% (95%CI 51–72%) (P=0.0003), respectively. In multivariate analysis, both autologous stem cell transplantation and period of progression/relapse affected event free and overall survival. Conclusions Regardless of front-line rituximab exposure, this study supports incorporating autologous stem cell transplantation in the therapeutic approach at first relapse for follicular lymphoma patients. PMID:21486862

Addition of rituximab to chop does not increase the risk of cardiotoxicity in patients with non-Hodgkin's lymphoma.

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Kilickap, Saadettin; Yavuz, Bunyamin; Aksoy, Sercan; Sahiner, Levent; Dincer, Murat; Harputluoglu, Hakan; Erman, Mustafa; Aytemir, Kudret; Tokgozoglu, Lale; Barista, Ibrahim

2008-01-01

The addition of rituximab to doxorubicin-containing standard chemotherapy significantly improves response to therapy and reduces the risk of death in B-cell non-Hodgkin's lymphoma (NHL) patients. However, the impact of this approach on doxorubicin-induced cardiotoxicity has not been elucidated. Patients who had been planned to receive CHOP or rituximab plus CHOP (R-CHOP) combination chemotherapy with a diagnosis of NHL were included in the study. In all patients, systolic and diastolic parameters were measured by using conventional and pulsed-wave tissue Doppler echocardiography, which is more sensitive than conventional lead-dependent techniques, both before and in the sixth month of therapy. There were 28 (M/F; 14/14) patients on CHOP and 33 (M/F; 16/17) patients on R-CHOP. Median age in CHOP and R-CHOP was 49 and 50 years (P = 0.44), respectively. Cumulative doxorubicin doses were 280 and 286 mg/m(2) on CHOP and R-CHOP (P = 0.65), respectively. None of the patients developed clinically evident congestive heart failure. Parameters of systolic function such as LVEF and FS did not significantly change in any patients. In both arms, tissue Doppler parameters of diastolic function such as lateral E and septal E velocity of mitral annulus decreased significantly after therapy (P 0.05). Conventional Doppler echocardiography yielded consistent findings. Both CHOP and R-CHOP cause diastolic dysfunction in the early period following their administration. The addition of rituximab to CHOP chemotherapy does not significantly increase the risk of doxorubicin-induced cardiotoxicity during this period.

Is Efficacy of the Anti-Cd20 Antibody Rituximab Preventing Hemolysis Due to Passenger Lymphocyte Syndrome?

Science.gov (United States)

Tsujimura, Kazuma; Ishida, Hideki; Tanabe, Kazunari

2017-02-01

Passenger lymphocyte syndrome (PLS) often occurs after ABO-mismatched solid organ and/or bone marrow transplantation between a donor and recipient. Viable donor B-lymphocytes transferred during organ transplantation produce antibodies against recipient red cell antigens, leading to hemolysis. The incidence of PLS has been reported to be around 9% after renal transplantation. A previous report showed that rituximab (Rit) was useful for treatment of PLS in allogeneic stem cell transplantation, bowel transplant and severe cases of hemolysis. However, the effectiveness of Rit in preventing PLS after renal transplantation has not yet been evaluated. The participants in this study were 85 patients who had undergone ABO-mismatched renal transplantation from January 2005 to April 2013. Rit was administered to these patients before transplantation. None of the patients that received Rit treatment developed PLS. Thus administration of Rit before transplantation effectively controlled the production of antibodies by B-lymphocytes, which probably prevented the development of PLS. © 2016 International Society for Apheresis, Japanese Society for Apheresis, and Japanese Society for Dialysis Therapy.

Addition of Rituximab to Involved-Field Radiation Therapy Prolongs Progression-free Survival in Stage I-II Follicular Lymphoma: Results of a Multicenter Study

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Ruella, Marco [Division of Haematology and Cell Therapy, Mauriziano Hospital and University of Torino, Torino (Italy); Center for Cellular Immunotherapies, Perelman School of Medicine, University of Pennsylvania, Philadelphia (United States); Filippi, Andrea Riccardo [Department of Oncology, Radiation Oncology, University of Torino, Torino (Italy); Bruna, Riccardo [Division of Haematology and Cell Therapy, Mauriziano Hospital and University of Torino, Torino (Italy); Di Russo, Anna [Radiation Oncology, Istituto Nazionale Tumori, Milano (Italy); Magni, Michele [Division of Medical Oncology, Istituto Nazionale Tumori, and University of Milano, Milano (Italy); Caracciolo, Daniele [Division of Haematology, San Giovanni Battista Hospital and University of Torino, Torino (Italy); Passera, Roberto [Division of Nuclear Medicine, San Giovanni Battista Hospital and University of Torino, Torino (Italy); Matteucci, Paola; Di Nicola, Massimo [Division of Medical Oncology, Istituto Nazionale Tumori, and University of Milano, Milano (Italy); Corradini, Paolo [Division of Haematology, Istituto Nazionale Tumori, and University of Milano, Milano (Italy); Parvis, Guido [Division of Haematology, San Luigi Gonzaga Hospital, Orbassano, Torino (Italy); Gini, Guido; Olivieri, Attilio [Division of Haematology, Ospedali Riuniti, Ancona (Italy); Ladetto, Marco [Division of Haematology, San Giovanni Battista Hospital and University of Torino, Torino (Italy); Ricardi, Umberto [Department of Oncology, Radiation Oncology, University of Torino, Torino (Italy); Tarella, Corrado, E-mail: corrado.tarella@gmail.com [Division of Haematology and Cell Therapy, Mauriziano Hospital and University of Torino, Torino (Italy); Hemato-Oncology Division, European Institute of Oncology, Milano (Italy); Devizzi, Liliana [Division of Medical Oncology, Istituto Nazionale Tumori, and University of Milano, Milano (Italy)

2016-03-15

Purpose: Rituximab (Rit) therapy added to involved-field radiation therapy (RT) has been proposed as an effective treatment for stage I-II follicular lymphoma (FL). The results of an observational multicenter study on the Rit-RT combination in limited-stage FL are here reported. Methods and Materials: Data have been collected from 2 consecutive cohorts of 94 patients with stage I-II FL treated between 1985 and 2011 at 5 Italian institutions. All patients had grade 1-3a FL, a median age of 54 years (range: 25-82). The first 51 patients received RT alone (control group), while the subsequent series of 43 patients received 4 rituximab courses (375 mg/m{sup 2}, days 1, 8, 15, 22) before RT (Rit-RT). Molecular disease was evaluated by nested bcl-2/IgH PCR or clonal IgH rearrangement was available in 33 Rit-RT patients. Results: At a median follow-up of 10.9 years (range: 1.8-22.9), the 10-year progression-free survival (PFS) and overall survival (OS) projections for the whole cohort were 57% and 87.5%, respectively. The 10-year PFS was significantly longer (P<.05) in the Rit-RT group (64.6%) compared to RT alone (50.7%), whereas the 10-year OS projections were not significantly different. On bivariate analysis controlling for stage, there was only a trend toward improved PFS for Rit-RT (HR, 0.55; P=.081). Follicular lymphoma international prognostic index and age were associated with OS but not with PFS on Cox regression analysis. Bone marrow molecular analysis showing PCR positivity at diagnosis was strongly associated with relapse risk upon univariate and multivariate analysis. Conclusions: This multicenter observational study suggests a potential benefit of adding rituximab to radiation therapy for stage I-II FL. The results of the currently ongoing randomized studies are required to confirm these results. The study underlines the importance of molecular disease monitoring also for patient with limited-stage disease.

Addition of Rituximab to Involved-Field Radiation Therapy Prolongs Progression-free Survival in Stage I-II Follicular Lymphoma: Results of a Multicenter Study

International Nuclear Information System (INIS)

Ruella, Marco; Filippi, Andrea Riccardo; Bruna, Riccardo; Di Russo, Anna; Magni, Michele; Caracciolo, Daniele; Passera, Roberto; Matteucci, Paola; Di Nicola, Massimo; Corradini, Paolo; Parvis, Guido; Gini, Guido; Olivieri, Attilio; Ladetto, Marco; Ricardi, Umberto; Tarella, Corrado; Devizzi, Liliana

2016-01-01

Purpose: Rituximab (Rit) therapy added to involved-field radiation therapy (RT) has been proposed as an effective treatment for stage I-II follicular lymphoma (FL). The results of an observational multicenter study on the Rit-RT combination in limited-stage FL are here reported. Methods and Materials: Data have been collected from 2 consecutive cohorts of 94 patients with stage I-II FL treated between 1985 and 2011 at 5 Italian institutions. All patients had grade 1-3a FL, a median age of 54 years (range: 25-82). The first 51 patients received RT alone (control group), while the subsequent series of 43 patients received 4 rituximab courses (375 mg/m"2, days 1, 8, 15, 22) before RT (Rit-RT). Molecular disease was evaluated by nested bcl-2/IgH PCR or clonal IgH rearrangement was available in 33 Rit-RT patients. Results: At a median follow-up of 10.9 years (range: 1.8-22.9), the 10-year progression-free survival (PFS) and overall survival (OS) projections for the whole cohort were 57% and 87.5%, respectively. The 10-year PFS was significantly longer (P<.05) in the Rit-RT group (64.6%) compared to RT alone (50.7%), whereas the 10-year OS projections were not significantly different. On bivariate analysis controlling for stage, there was only a trend toward improved PFS for Rit-RT (HR, 0.55; P=.081). Follicular lymphoma international prognostic index and age were associated with OS but not with PFS on Cox regression analysis. Bone marrow molecular analysis showing PCR positivity at diagnosis was strongly associated with relapse risk upon univariate and multivariate analysis. Conclusions: This multicenter observational study suggests a potential benefit of adding rituximab to radiation therapy for stage I-II FL. The results of the currently ongoing randomized studies are required to confirm these results. The study underlines the importance of molecular disease monitoring also for patient with limited-stage disease.

Ibrutinib, lenalidomide, and rituximab in relapsed or refractory mantle cell lymphoma (PHILEMON): a multicentre, open-label, single-arm, phase 2 trial.

Science.gov (United States)

Jerkeman, Mats; Eskelund, Christian Winther; Hutchings, Martin; Räty, Riikka; Wader, Karin Fahl; Laurell, Anna; Toldbod, Helle; Pedersen, Lone Bredo; Niemann, Carsten Utoft; Dahl, Christina; Kuitunen, Hanne; Geisler, Christian H; Grønbæk, Kirsten; Kolstad, Arne

2018-03-01

Regimens based on ibrutinib alone and lenalidomide and rituximab in combination show high activity in patients with relapsed or refractory mantle cell lymphoma. We hypothesised that the combination of all three drugs would improve efficacy compared with previously published data on either regimen alone. In this multicentre, open-label, single-arm, phase 2 trial, we enrolled patients aged 18 years or older with relapsed or refractory mantle cell lymphoma who had previously been treated with at least one rituximab-containing regimen, an Eastern Cooperative Oncology Group performance status score of 0-3, and at least one site of measurable disease, and who met criteria for several laboratory-assessed parameters. Treatment was divided into an induction phase of 12 cycles of 28 days with all three drugs and a maintenance phase with ibrutinib and rituximab only (cycle duration 56 days), given until disease progression or unacceptable toxicity. In the induction phase, patients received intravenous (375 mg/m 2 ) or subcutaneous (1400 mg) rituximab once a week during cycle 1 and then once every 8 weeks. Oral ibrutinib (560 mg once a day) was given to patients every day in the cycle, whereas oral lenalidomide (15 mg once a day) was given on days 1-21. The primary endpoint was overall response assessed in the intention-to-treat population according to Lugano criteria. Safety analysis included all patients who received the treatment, irrespective of eligibility or duration of treatment. The trial is ongoing, but is no longer accruing patients, and is registered with ClinicalTrials.gov, number NCT02460276. Between April 30, 2015, and June 1, 2016, we enrolled 50 patients with relapsed or refractory mantle cell lymphoma at ten centres in Sweden, Finland, Norway, and Denmark. At a median follow-up of 17·8 months (IQR 14·7-20·9), 38 (76%, 95% CI 63-86) patients had an overall response, including 28 (56%, 42-69) patients who had a complete response and ten (20%, 11-33) who had a

Chemoimmunotherapy for relapsed/refractory and progressive 17p13-deleted chronic lymphocytic leukemia (CLL) combining pentostatin, alemtuzumab, and low-dose rituximab is effective and tolerable and limits loss of CD20 expression by circulating CLL cells.

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Zent, Clive S; Taylor, Ronald P; Lindorfer, Margaret A; Beum, Paul V; LaPlant, Betsy; Wu, Wenting; Call, Timothy G; Bowen, Deborah A; Conte, Michael J; Frederick, Lori A; Link, Brian K; Blackwell, Sue E; Veeramani, Suresh; Baig, Nisar A; Viswanatha, David S; Weiner, George J; Witzig, Thomas E

2014-07-01

Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL) patients with purine analog refractory disease or TP53 dysfunction still have limited treatment options and poor survival. Alemtuzumab-containing chemoimmunotherapy regimens can be effective but frequently cause serious infections. We report a Phase II trial testing the efficacy and tolerability of a short-duration regimen combining pentostatin, alemtuzumab, and low-dose high-frequency rituximab designed to decrease the risk of treatment-associated infections and to limit the loss of CD20 expression by CLL cells. The study enrolled 39 patients with progressive CLL that was either relapsed/refractory (n = 36) or previously untreated with 17p13 deletion (17p13-) (n = 3). Thirteen (33%) patients had both 17p13- and TP53 mutations predicted to be dysfunctional, and eight patients had purine analog refractory CLL without TP53 dysfunction. Twenty-six (67%) patients completed therapy, with only five (13%) patients having treatment-limiting toxicity and no treatment-related deaths. Twenty-two (56%) patients responded to treatment, with 11 (28%) complete responses (four with incomplete bone marrow recovery). Median progression-free survival was 7.2 months, time to next treatment was 9.1 months, and overall survival was 34.1 months. The majority of deaths (82%) were caused by progressive disease, including transformed diffuse large B-cell lymphoma (n = 6). Correlative studies showed that low-dose rituximab activates complement and natural killer cells without a profound and sustained decrease in expression of CD20 by circulating CLL cells. We conclude that pentostatin, alemtuzumab, and low-dose high-frequency rituximab is a tolerable and effective therapy for CLL and that low-dose rituximab therapy can activate innate immune cytotoxic mechanisms without substantially decreasing CD20 expression. © 2014 Wiley Periodicals, Inc.

Severe antiphospholipid antibody syndrome - response to plasmapheresis and rituximab.

Science.gov (United States)

Gkogkolou, Paraskevi; Ehrchen, Jan; Goerge, Tobias

2017-09-01

Antiphospholipid antibody syndrome (APS) is a systemic autoimmune disease characterized by arterial and/or venous thrombosis, recurrent abortions and detection of antiphospholipid antibodies. In fulminant cases, involvement of multiple organs can lead to significant morbidity and even fatal outcomes, so that a rapid, interdisciplinary treatment is needed. Here, we describe the case of a 39-year-old woman with a severe hard-to-treat APS with arterial occlusion and progressive skin necrosis, who was successfully treated with a combination therapy with plasmapheresis and rituximab. The treatment led to complete remission of the skin lesions for over a year. Clinical response correlated with a long-lasting reduction of antiphospholipid antibodies and B-cell depletion. This case demonstrates the use of antiphospholipid antibodies for monitoring APS-activity and shows that this severe vascular disease requires rigorous therapeutic approaches.

Rituximab in the treatment of refractory or relapsing eosinophilic granulomatosis with polyangiitis (Churg-Strauss syndrome).

Science.gov (United States)

Thiel, Jens; Hässler, Fabian; Salzer, Ulrich; Voll, Reinhard E; Venhoff, Nils

2013-09-24

Eosinophilic granulomatosis with polyangiitis (EGPA) is part of antineutrophil cytoplasmic antibodies (ANCAs)-associated vasculitides. In EGPA small-vessel vasculitis is associated with eosinophilia and asthma. About 40% of EGPA patients are ANCA-positive, suggesting a role for B cells in the pathogenesis of EGPA. B cell-depleting therapy with rituximab (RTX) can be effective in ANCA-positive EGPA, but very few patients have been published to date. The role of RTX in the treatment of ANCA-negative EGPA is unclear. We report a single-center cohort of patients with eosinophilic granulomatosis with polyangiitis. Of these patients, nine (six ANCA-positive, three ANCA-negative) had been treated with RTX for relapsing or refractory disease on standard immunosuppressive treatment. In a retrospective analysis, data on treatment response, frequency of relapses, adverse events, and peripheral B-cell reconstitution were evaluated. Furthermore, serum immunoglobulin concentrations, ANCA status, and peripheral B cell subpopulations were assessed after RTX treatment. All patients had high disease activity before RTX treatment. At presentation 3 months after RTX therapy, all ANCA-positive and ANCA-negative patients had responded to RTX, with one patient being in complete remission, and eight patients being in partial remission. After a mean follow-up of 9 months, C-reactive protein concentrations had normalized, eosinophils had significantly decreased, and prednisone had been tapered in all patients. In all patients, RTX therapy was combined with a standard immunosuppressive therapy. Within the 9-month observation period, no relapse was recorded. Three patients were preemptively retreated with RTX, and during the median follow-up time of 3 years, no relapse occurred in these patients. During the follow-up of 13 patient-years, five minor but no major infections were recorded. In our analysis on nine patients with EGPA resistant to standard therapy, rituximab proved to be an

Quiste dermoide intracraneal con rotura espontánea. Reporte de caso

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Leonardo Andrés Chacón-Zambrano

2017-04-01

Full Text Available Introducción: Los quistes dermoides son tumores raros, que se originan por la inclusión de elementos de origen ectodérmico en el momento del cierre del tubo neural durante la embriogénesis. Su contenido incluye una variedad de derivados del ectodermo como glándulas apocrinas, sudor, quistes sebáceos, folículos pilosos, epitelio escamoso y dientes. Los síntomas que generan estos tumores benignos son tanto por el efecto de masa sobre las estructuras neurovasculares adyacentes (cefalea, convulsiones, hidrocefalia, isquemia, como por la irritación meníngea en los casos de ruptura hacia el espacio subaracnoideo. Objetivo: Presentar el curso clínico de paciente femenino de 21 años de edad, que acude a la consulta de neurocirugía con clínica de cefalea y síncope. Presentación del caso: Paciente con rotura espontánea de un quiste dermoide intracraneal que consultaba previamente por clínica de cefalea, a la cual se asocia más recientemente episodios de alteración de la conciencia, realizándose estudio de neuroimágenes con evidencia de quiste dermoide intracraneal roto, el cual fue manejado quirúrgicamente con resolución exitosa de la sintomatología. Conclusiones: Se considera relevante el caso teniendo en cuenta lo inusual de la patología según la epidemiología consultada, además este reporte de caso, permite sensibilizar al personal de salud sobre esta patología tumoral la cual puede llegar a la cura en caso de resección quirúrgica completa, con resolución de la clínica.

Addition of rituximab to chemotherapy overcomes the negative prognostic impact of cyclin E expression in diffuse large B-cell lymphoma

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Frei, E; Visco, C; Xu-Monette, Z Y

2013-01-01

High levels of cyclin E (CCNE) are accompanied by shorter survival in cyclophosphamide, hydroxydaunorubicin, oncovin and prednisone (CHOP)-treated diffuse large B-cell lymphomas (DLBCL), independent of the international prognostic index (IPI). Data on the prognostic role of CCNE in the 'rituximab...

Rituximab Effectiveness and Safety for Treating Primary Sjögren's Syndrome (pSS: Systematic Review and Meta-Analysis.

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Francine Bertolais do Valle Souza

Full Text Available Primary Sjögren's Syndrome (pSS is a systemic autoimmune disease that involves the exocrine glands and internal organs. pSS leads to destruction and loss of secretory function due to intense lymphoplasmacytic infiltration. Therapeutic options include mainly symptomatic and supportive measures, and traditional immunosuppressant drugs have shown no effectiveness in randomized trials. Rituximab (RTX is a chimeric antibody anti-CD20 that leads to B cell depletion by diverse mechanisms. There is evidence that this drug may be effective for treating pSS. The objective of this systematic review was to evaluate Rituximab effectiveness and safety for treating pSS.We conducted a systematic review of RCTs published until December 2015, with no language restriction. We registered a protocol on Plataforma Brasil (40654814.6.0000.5505 and developed search strategies for the following scientific databases: MEDLINE, EMBASE, CENTRAL and LILACS. We included adults with established pSS diagnosis and considered the use of Rituximab as intervention and the use of other drugs or placebo as control. Four studies met our eligibility criteria: three with low risk of bias and one with uncertain risk of bias. The total number of participants was 276 (145 RTX, 131 placebo. We assessed the risk of bias of each included study and evaluated the following as primary outcomes: lacrimal gland function, salivary gland function, fatigue improvement and adverse events. We found no significant differences between the groups in the Schirmer test at week 24 meta-analysis (MD 3.59, 95% CI -2.89 to 10.07. Only one study evaluated the lissamine green test and reported a statistically significant difference between the groups at week 24 (MD -2.00, 95% CI -3.52 to -0.48. There was a significant difference between the groups regarding salivary flow rate (MD 0.09, 95% CI 0.02 to 0.16 and improvement in fatigue VAS at weeks 6 (RR 3.98, 95% CI 1.61 to 9.82 and week 16 (RR 3.08, 95% CI 1.21 to

THE ECSTACY OF GOLD Patent Expirations for Trastuzumab, Bevacizumab, Rituximab, and Cetuximab.

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Serna-Gallegos, Tasha R; LaFargue, Christopher J; Tewari, Krishnansu S

2017-11-22

Fully humanized monoclonal antibodies have revolutionized the treatment of many solid tumors, including breast, lung, colorectal, and ovarian cancer. Among the most widely used monoclonal antibodies in clinical oncology are cetuximab, trastuzumab, rituximab, and bevacizumab. This article will review these four notable monoclonal antibodies, their role in clinical oncology, and the drug patents that are nearing expiration. They are used in both first and second line treatment regimens for multiple common malignancies. With recent patent expirations, pharmaceutical companies involved in biosimilar manufacture are looking to establish ownership over these financial monopolies. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Favorable outcome of Epstein-Barr virus-associated B-cell lymphoproliferative disorder complicated by immunoglobulin G4-related disease treated with rituximab-based therapy: a case report.

Science.gov (United States)

Ueda, Koki; Ikeda, Kazuhiko; Ogawa, Kazuei; Sukegawa, Masumi; Sano, Takahiro; Kimura, Satoshi; Suzuki, Osamu; Hashimoto, Yuko; Takeishi, Yasuchika

2016-08-24

After acute infection of Epstein-Barr virus, Epstein-Barr virus-infected B cells survive but usually do not show clonal proliferation. However, Epstein-Barr virus-infected B cells occasionally acquire a proliferative capacity that provokes clonal lymphoproliferative disorders. We herein present a case with Epstein-Barr virus-infected CD30+ B cell and immunoglobulin G4+ plasmacytoid cell proliferation in the lymph nodes, suggesting a pathological and clinical interaction between Epstein-Barr virus-associated B-cell lymphoproliferative disorders and immunoglobulin G4-related disease. Immunoglobulin G4-related disease has been recognized as a benign disease with proliferation of IgG4-related disease+ plasmacytoid cells. Several studies have recently reported the coexistence of immunoglobulin G4-related disease+ plasmacytoid cells with Epstein-Barr virus-infected B cells in lymph nodes in some immunoglobulin G4-related disease cases. However, the pathogenic role of the clonal proliferation of Epstein-Barr virus-infected B cells in immunoglobulin G4-related disease, as well as the treatments for patients with both Epstein-Barr virus-infected B cells and immunoglobulin G4-related disease, have never been discussed. A 50-year-old Japanese man was referred to us for persistent fatigue and lymphadenopathy. His blood examination showed elevated IgG4, and detected high levels of Epstein-Barr virus DNA. A lymph node biopsy revealed IgG4+ plasmacytoid cells and infiltration of large lymphoid cells, which were positive for CD20, CD30, Epstein-Barr virus-related late membrane protein 1, and Epstein-Barr virus-encoded RNA, and were negative for IgG4. Based on the diagnosis of both Epstein-Barr virus-associated B-cell lymphoproliferative disorder and IgG4-related disease, the patient received eight cycles of rituximab combined with cyclophosphamide and prednisolone, which resulted in the complete disappearance of lymphadenopathy. Moreover, his serum IgG4 level was significantly

Spotlight on rituximab in the treatment of antineutrophil cytoplasmic antibody-associated vasculitis: current perspectives

Directory of Open Access Journals (Sweden)

Moog P

2015-11-01

Full Text Available Philipp Moog, Klaus Thuermel Abteilung für Nephrologie, Klinikum rechts der Isar, Technische Universität München, Munich, Germany Abstract: A 54-year-old patient presented to his general practitioner because of strong muscle pain in both thighs. Inflammatory parameters (CRP 16.3 mg/dL and white blood cells (15 g/L were elevated. The patient reported a weight loss of 10 kg in 4 weeks. There was no fever or any other specific symptoms. Urine dipstick examination and computed tomography of the chest were unremarkable. Because of increasing symptoms, the patient was referred to our department. Magnetic resonance tomography showed diffuse inflammatory changes of the muscles of both thighs. Neurological examination and electrophysiology revealed axonal sensorimotor neuropathy and ground-glass opacities of both lungs had occurred. Serum creatinine increased to 229 µmol/L within a few days, with proteinuria of 3.3 g/g creatinine. Kidney biopsy showed diffuse pauci-immune proliferative glomerulonephritis. Proteinase 3-specific antineutrophil cytoplasmic antibodies were markedly increased. Birmingham Vasculitis Activity Score was 35. Within 2 days, serum creatinine further increased to 495 µmol/L. Plasma exchange, high-dose glucocorticosteroids, and hemodialysis were started. The patient received cyclophosphamide 1 g twice and rituximab 375 mg/m2 four times according to the RITUXVAS protocol. Despite ongoing therapy, hemodialysis could not be withdrawn and had to be continued over 3 weeks until diuresis normalized. Glucocorticosteroids were tapered to 20 mg after 2 months, and serum creatinine was 133 µmol/L. However, nephritic urinary sediment reappeared. Another dose of 1 g cyclophosphamide was given, and glucocorticosteroids were raised for another 4 weeks. After 6 months, the daily prednisolone dose was able to be tapered to 5 mg. Serum creatinine was 124 µmol/L, proteinuria further decreased to 382 mg/g creatinine, and the Birmingham

Long-term Follow-up of Treatment with Ibrutinib and Rituximab in Patients with High-Risk Chronic Lymphocytic Leukemia.

Science.gov (United States)

Jain, Preetesh; Keating, Michael J; Wierda, William G; Sivina, Mariela; Thompson, Philip A; Ferrajoli, Alessandra; Estrov, Zeev; Kantarjian, Hagop; O'Brien, Susan; Burger, Jan A

2017-05-01

Background: Ibrutinib is an active therapy with an acceptable safety profile for patients with chronic lymphocytic leukemia (CLL), including high-risk patients with del17p or with TP53 mutations. Ibrutinib is broadly indicated for the treatment of patients with CLL and specifically including those with 17p deletion. The optimal use of ibrutinib in combination with other agents remains controversial. Experimental Design: We report the long-term outcome [median follow-up of 47 months (range, 36-51 months)] of 40 patients with high-risk CLL, treated on the first ibrutinib combination trial with rituximab (IR). The majority of patients (36/40) were previously treated. Results: Median age was 65 years, and 21 patients (52%) had 17p deletion. Median duration on treatment was 41 months (range, 2-51 months), and median number of treatment cycles was 42 (range, 2-49). Overall response rate was 95%, and 9 patients (23%) attained a complete remission. Twenty-one patients discontinued treatment, 10 due to disease progression, 9 for other causes, and 2 due to stem cell transplantation; the remaining 19 patients continue on ibrutinib. Median progression-free survival for all patients was 45 months, which was significantly shorter in the subgroup of patients with del17p ( n = 21, 32.3 months, P = 0.02). Fourteen patients (35%) died, five from progressive disease, five from infections, and four from other causes. Median overall survival has not been reached. Conclusions: IR combination therapy leads to durable remissions in high-risk CLL; the possible benefit from the addition of rituximab is currently explored in a randomized trial. Clin Cancer Res; 23(9); 2154-8. ©2016 AACR . ©2016 American Association for Cancer Research.

Study of conjugation and radiolabeling of monoclonal antibody rituximab for use in radionuclide therapy

International Nuclear Information System (INIS)

Massicano, Adriana Vidal Fernandes

2011-01-01

Lymphomas are tumors originated from the transformation of a lymphocyte in the lymphatic system. The most common lymphoma is the Non-Hodgkin Lymphoma (NHL). Advances in immunology and molecular biology have been improving NHL's detection and treatment strategies development, such as Radioimmunotherapy (RIT). Rituximab is an anti-CD20 monoclonal antibody used as immunotherapeutic to treat refractory or relapsed NHL. The goal of the present work was to conjugate this antibody to DOTA-NHS-ester bifunctional chelator and to radiolabel it with 177 Lu radioisotope in order to develop a radio immunotherapeutic agent for NHL's treatment. Different rituximab to DOTA molar ratios (1:5, 1:10, 1:20, 1:50, 1:250, 1:500 and 1:1000) were evaluated in order to determine the best condition for obtaining the highest radiochemical purity of radio immunotherapeutic. The stability of the unlabeled immuno conjugated was evaluated by high performance liquid chromatography (HPLC) for up to 240 days in different storage conditions. The stability of the labeled preparations was evaluated either after storing at 2-8 degree C or incubation in human serum at 37 degree C. The binding to serum proteins was also determined. In vivo studies were performed in healthy Swiss mice, in order to characterize the biological properties of labeled conjugate. Finally, preliminary studies of radio immuno conjugated competitive binding to CD20 positive Raji cells were carried out in order to analyze if the process of conjugation and radiolabeling compromises the immunoreactivity of the antibody. The conjugation applying lower antibody to chelator molar ratios (1:5, 1:10 and 1:20) showed high stability when stored for up to 240 days in different conditions. The HPLC analysis showed that the monoclonal antibody conjugated in molar ratio 1:50 was labeled with higher radiochemical purity (> 95%) when purified in PD-10 column. This conjugate showed reasonable stability at 2-8 degree C. The analysis of the

B-cell depletion with rituximab in the treatment of autoimmune diseases. Graves' ophthalmopathy the latest addition to an expanding family

DEFF Research Database (Denmark)

Nielsen, Claus H; El Fassi, Daniel; Hasselbalch, Hans K

2007-01-01

of 10 Graves' disease patients remained in remission 400 days after rituximab treatment versus none in the control group, and remarkable improvements in the eye symptoms of patients with Graves' ophthalmopathy were observed. This supports a role for B cells in the pathogenesis of Graves' ophthalmopathy...

ABO-Incompatible Adult Living Donor Liver Transplantation Under the Desensitization Protocol With Rituximab.

Science.gov (United States)

Song, G-W; Lee, S-G; Hwang, S; Kim, K-H; Ahn, C-S; Moon, D-B; Ha, T-Y; Jung, D-H; Park, G-C; Kim, W-J; Sin, M-H; Yoon, Y-I; Kang, W-H; Kim, S-H; Tak, E-Y

2016-01-01

ABO incompatibility is no longer considered a contraindication for adult living donor liver transplantation (ALDLT) due to various strategies to overcome the ABO blood group barrier. We report the largest single-center experience of ABO-incompatible (ABOi) ALDLT in 235 adult patients. The desensitization protocol included a single dose of rituximab and total plasma exchange. In addition, local graft infusion therapy, cyclophosphamide, or splenectomy was used for a certain time period, but these treatments were eventually discontinued due to adverse events. There were three cases (1.3%) of in-hospital mortality. The cumulative 3-year graft and patient survival rates were 89.2% and 92.3%, respectively, and were comparable to those of the ABO-compatible group (n = 1301). Despite promising survival outcomes, 17 patients (7.2%) experienced antibody-mediated rejection that manifested as diffuse intrahepatic biliary stricture; six cases required retransplantation, and three patients died. ABOi ALDLT is a feasible method for expanding a living liver donor pool, but the efficacy of the desensitization protocol in targeting B cell immunity should be optimized. © Copyright 2015 The American Society of Transplantation and the American Society of Transplant Surgeons.

Comparison of the efficacy of azathioprine and rituximab in neuromyelitis optica spectrum disorder

DEFF Research Database (Denmark)

Nikoo, Zahra; Badihian, Shervin; Shaygannejad, Vahid

2017-01-01

Neuromyelitis optica spectrum disorder (NMOSD) often follows a relapsing course. As disability in NMOSD is attack-related, effective treatments are needed. We aimed to compare the efficacy of azathioprine (AZA) and rituximab (RIT) as maintenance therapy in NMOSD patients. An open, randomized...... = 0–7). Patients were randomized into two groups, which did not differ according to age, gender distribution, and disease duration. In the AZA group, 35 patients [20 aquaporin-4 (AQP4)-IgG positive] were started on 50 mg/day oral AZA and increased to 2–3 mg/kg/day (with oral prednisolone as adjunctive...

Con Edison power failure of July 13 and 14, 1977. Final staff report

Energy Technology Data Exchange (ETDEWEB)

None

1978-06-01

On July 13, 1977 the entire electric load of the Con Edison system was lost, plunging New York City and Westchester County into darkness. The collapse resulted from a combination of natural events, equipment malfunctions, questionable system-design features, and operating errors. An attempt is made in this report to answer the following: what were the specific causes of the failure; if equipment malfunctions and operator errors contributed, could they have been prevented; to what extent was Con Edison prepared to handle such an emergency; and did Con Edison plan prudently reserve generation, for reserve transmission capability, for automatic equipment to protect its system, and for proper operator response to a critical situation. Following the introductory and summary section, additional sections include: the Consolidated Edison system; prevention of bulk power-supply interruptions; the sequence of failure and restoration; analysis of the July 1977 power failure; restoration sequence and equipment damage assessment; and other investigations of the blackout. (MCW)

Randomized Phase II Trial Comparing Obinutuzumab (GA101) With Rituximab in Patients With Relapsed CD20(+) Indolent B-Cell Non-Hodgkin Lymphoma

DEFF Research Database (Denmark)

Sehn, L. H.; Goy, A.; Offner, F. C.

2015-01-01

Purpose Obinutuzumab (GA101), a novel glycoengineered type II anti-CD20 monoclonal antibody, demonstrated responses in single-arm studies of patients with relapsed/refractory non-Hodgkin lymphoma. This is the first prospective, randomized study comparing safety and efficacy of obinutuzumab...... with rituximab in relapsed indolent lymphoma. The primary end point of this study was the overall response rate (ORR) in patients with follicular lymphoma after induction and safety in patients with indolent lymphoma. Patients and Methods A total of 175 patients with relapsed CD20(+) indolent lymphoma requiring...... maintenance therapy every 2 months for up to 2 years. Results Among patients with follicular lymphoma (n = 149), ORR seemed higher for obinutuzumab than rituximab (44.6% v 33.3%; P = .08). This observation was also demonstrated by a blinded independent review panel that measured a higher ORR for obinutuzumab...

RadCon: Parameter report focusing on Tropical and Subtropical environments in Australia

International Nuclear Information System (INIS)

Domel, R.U.; Crawford, J; Harris, F.; Twining, J.

2000-09-01

Models to simulate the transfer of radionuclides through air, water and terrestrial ecosystems have been developed and used regularly over the last 20 years. RadCon was developed as a simple model to assess the radiological consequences, as dose, to humans of short-term depositions of radionuclides. Internal exposure via inhalation and ingestion are included in this model as well as external exposure from the passing cloud (cloud shine) and from radioactivity deposited on the ground (ground shine).Initially, the RadCon model will deal with the Australian and South East Asian region but flexibility has been incorporated into the design to allow application in other regions. In a manner similar to a geographic information system, the display of input and output data allows quick access to the results, both numerically and graphically. Coloured concentration gradients, stepping through time, are superimposed on the area of interest to present atmospheric and ground concentrations of the radionuclides and, after the calculations, human dose. The model has portability across computer platforms.This report summarises the parameters and some of the transfer factors underlying the calculations. While the focus was on the tropical and subtropical regions in Australia, for many parameters the values may only have been available for temperate regions, in which case this has been used as the default value. The parameter flexibility is a major aspect of this model and a report to describe the editor has been written (Crawford and Domel, ANSTO/M-129). The aim of this document is to chronologically expand on the formulae and parameter tables presented in the Technical Guide (Crawford et al., ANSTO/E-744, May 2000). The two documents should be read together with the Technical Guide presenting the mathematical computations and this report presenting some of the input values used to calculate the end-point results from the computations. A User Guide to assist in the implementation

Lymphomatoid granulomatosis of central nervous system and lung driven by epstein barr virus proliferation: successful treatment with rituximab-containing chemotherapy.

Science.gov (United States)

Fernandez-Alvarez, Ruben; Gonzalez, Me; Fernandez, Almudena; Gonzalez-Rodriguez, Ap; Sancho, Jm; Dominguez, Francisco; Fernandez, Carmen

2014-01-01

Lymphomatoid granulomatosis (LYG) is a very rare Epstein-Barr virus (EBV) associated B-cell lymphoproliferative disorder. We report the case of a 41-year-old man who presented with fever and respiratory symptoms. Computed tomography showed multiple nodules in both lung fields. Polymerase chain reaction (PCR) analysis for EBV was positive in bronchoalveolar lavage and biopsy of lung node yielded a diagnosis of LYG, grade III. Shortly after initiation of treatment with agressive chemotherapy, neurological deterioration appeared. Neuroimaging findings revealed hydrocephalus and PCR analysis of the cerebrospinal fluid (CSF) was positive for EBV. Treatment with intravenous rituximab led to rapid reduction of EBV load in CSF, along with clinical and radiological improvement. After completion of treatment with immunochemotherapy, an autologous stem cell transplantation was performed. Patient stays in remission 18 months after diagnosis.

Prolonged extracorporeal membrane oxygenation therapy for severe acute respiratory distress syndrome in a child affected by rituximab-resistant autoimmune hemolytic anemia: a case report

Directory of Open Access Journals (Sweden)

Beretta Chiara

2009-04-01

Full Text Available Abstract Introduction Autoimmune hemolytic anemia in children younger than 2 years of age is usually characterized by a severe course, with a mortality rate of approximately 10%. The prolonged immunosuppression following specific treatment may be associated with a high risk of developing severe infections. Recently, the use of monoclonal antibodies (rituximab has allowed sustained remissions to be obtained in the majority of pediatric patients with refractory autoimmune hemolytic anemia. Case presentation We describe the case of an 8-month-old Caucasian girl affected by a severe form of autoimmune hemolytic anemia, which required continuous steroid treatment for 16 months. Thereafter, she received 4 weekly doses of rituximab (375 mg/m2/dose associated with steroid therapy, which was then tapered over the subsequent 2 weeks. One month after the last dose of rrituximab, she presented with recurrence of severe hemolysis and received two more doses of rrituximab. The patient remained in clinical remission for 7 months, before presenting with a further relapse. An alternative heavy immunosuppressive therapy was administered combining cyclophosphamide 10 mg/kg/day for 10 days with methylprednisolone 40 mg/kg/day for 5 days, which was then tapered down over 3 weeks. While still on steroid therapy, the patient developed an interstitial pneumonia with Acute Respiratory Distress Syndrome, which required immediate admission to the intensive care unit where extracorporeal membrane oxygenation therapy was administered continuously for 37 days. At 16-month follow-up, the patient is alive and in good clinical condition, with no organ dysfunction, free from any immunosuppressive treatment and with a normal Hb level. Conclusions This case shows that aggressive combined immunosuppressive therapy may lead to a sustained complete remission in children with refractory autoimmune hemolytic anemia. However, the severe life-threatening complication presented by our

Rituximab treatment for relapsed opsoclonus-myoclonus syndrome.

Science.gov (United States)

Toyoshima, Daisaku; Morisada, Naoya; Takami, Yuichi; Kidokoro, Hiroyuki; Nishiyama, Masahiro; Nakagawa, Taku; Ninchoji, Takeshi; Nozu, Kandai; Takeshima, Yasuhiro; Takada, Satoshi; Nishio, Hisahide; Iijima, Kazumoto

2016-03-01

Opsoclonus-myoclonus syndrome (OMS) is a rare neurological disorder that is associated with paraneoplastic diseases. Because OMS can frequently relapse, patients may be inflicted with neurological problems for a long time. Recently, rituximab (RTX) was introduced as a drug to treat OMS. To assess RTX treatment, we studied a patient who experienced recurrence of OMS. A 2-year-old Japanese boy, who had left adrenal neuroblastoma, suddenly showed OMS symptoms, including ataxia and opsoclonus. Surgical resection of the tumor and subsequent steroid therapy ameliorated his symptoms. When OMS relapsed during the time when prednisolone was reduced, he was treated with full-dose RTX therapy (375 mg/m2/week) for 4 consecutive weeks. However, 1year later, he presented again with OMS symptoms. This time, we only administered an additional single dose of RTX treatment (375 mg/m2), allowing remission of OMS symptoms. During 2 years after the additional RTX treatment, OMS symptoms did not appear, even when prednisolone was reduced. He had no adverse events associated with RTX during the whole treatment period. An additional single-dose RTX therapy might be effective for relapsed OMS patients who were previously treated with full-dose RTX therapy. Copyright © 2015 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

Successful plasma exchange combined with rituximab therapy in aggressive APS-related cutaneous necrosis.

Science.gov (United States)

Costa, Rubens; Fazal, Salman; Kaplan, Robert B; Spero, Joel; Costa, Ricardo

2013-03-01

Antiphospholipid antibody syndrome (APS) is a systemic autoimmune disorder characterized by venous and/or arterial thrombosis or recurrent fetal loss associated with the presence of antiphospholipid antibodies and/or a lupus anticoagulant. The skin appears to be an important target organ and many cases of APS may present with skin manifestations. These lesions may be manifold and may take the form of livedo reticularis, livedo racemosa, ulcerations, digital gangrene, subungeal splinter hemorrhages, superficial venous thrombosis, thrombocytopenic purpura, pseudovasculitic manifestations, extensive cutaneous necrosis, or primary anetoderma. We report a case of fulminant APS-related cutaneous necrosis. A 38-year-old Caucasian male with a past history of APS, multiple deep vein thrombi/pulmonary emboli, presented with necrotic lesions on his right upper and right lower extremities. Initially, baseline anticoagulation was increased without improvement. Subsequently, plasma exchange was initiated on a daily schedule. Furthermore, rituximab 1,000 mg IV was administered on days 1 and 15. After six consecutive daily sessions of plasma exchange, there was significant regression of the necrotic lesions. After a 22-day hospital stay, the patient was discharged to home on fondaparinux. The patient presented approximately 2 months later after missing follow-up appointments. At the time, his initial lesions looked remarkably improved.

The incidence of biopsy-proven transformation in follicular lymphoma in the rituximab era. A retrospective analysis from the Czech Lymphoma Study Group (CLSG) database.

Science.gov (United States)

Janikova, Andrea; Bortlicek, Zbynek; Campr, Vit; Kopalova, Natasa; Benesova, Katerina; Hamouzova, Michaela; Belada, David; Prochazka, Vit; Pytlik, Robert; Vokurka, Samuel; Pirnos, Jan; Duras, Juraj; Mocikova, Heidi; Mayer, Jiri; Trneny, Marek

2018-04-01

The aim of this study is to assess the incidence, risk factors, and outcome of biopsy-proven transformation in follicular lymphoma (FL) patients in the rituximab era. Transformation was analyzed in 1233 patients with initially diagnosed FL grades 1-3A, identified between 2002 and 2012 in the prospectively maintained Czech Lymphoma Study Group database. Only patients with histologically proven transformation (HT) were included. HT occurred in 58 cases at a median of 3.0 years from the initial FL diagnosis; the HT rate was 4% at 5 years. Transformation occurred most frequently at the first relapse (84% patients). Median OS from the HT was 2.5 years (95% CI 0.4-4.6) and 6-year OS with HT was shorter compared to all FLs (60 vs. 83.9%; 95% CI). A bulky tumor (≥ 10 cm), increased lactate dehydrogenase, age ≥ 60 years, and International Prognostic Index (intermediate/high risk), but not Follicular Lymphoma International Prognostic Index, were associated with transformation (p transformation rate at 5 years of 4.23% (95% CI 2.52-5.93); subsequent rituximab maintenance (n = 276) vs. observation (n = 153) was associated with a lower transformation rate (p.033; HR 3.29; CI 1.10-9.82). The transformation rate seems to be lower than in previous series, which may be influenced by broad use of rituximab, but prognosis of HT developed during therapy continues to be poor.

RadConEd: A Graphical Data Editor for the Radiological Consequences Model, RadCon

International Nuclear Information System (INIS)

Crawford, J.; Domel, R.U.

2000-05-01

This document describes the application, RadConEd, which has been designed and implemented to enable users of the RadCon system to update these parameter files. The RadCon system is written in the Java programming language, and as such provides portability across computer platforms. The software described in this report was developed in line with the portability requirements of RadCon, thus providing a uniform user interface across computer platforms and bypassing the need of using system editors. In addition a number of data integrity measures were implemented

Rituximab Maintenance Treatment of Relapsed/Resistant Follicular Non-Hodgkin's Lymphoma: Long-Term Outcome of the EORTC 20981 Phase III Randomized Intergroup Study

NARCIS (Netherlands)

van Oers, Marinus H. J.; van Glabbeke, Martine; Giurgea, Livia; Klasa, Richard; Marcus, Robert E.; Wolf, Max; Kimby, Eva; van 't Veer, Mars; Vranovsky, Andrej; Holte, Harald; Hagenbeek, Anton

2010-01-01

Purpose In 2006, we published the results of the European Organisation for Research and Treatment of Cancer phase III trial EORTC 20981 on the role of rituximab in remission induction and maintenance treatment of relapsed/resistant follicular lymphoma (FL). At that time, the median follow-up for the

Comparable Efficacy of Idelalisib Plus Rituximab and Ibrutinib in Relapsed/refractory Chronic Lymphocytic Leukemia: A Retrospective Case Matched Study of the Polish Adult Leukemia Group (PALG).

Science.gov (United States)

Puła, Bartosz; Budziszewska, Bożena Katarzyna; Rybka, Justyna; Gil, Lidia; Subocz, Edyta; Długosz-Danecka, Monika; Zawirska, Daria; Waszczuk-Gajda, Anna; Iskierka-Jażdżewska, Elżbieta; Kopacz, Agnieszka; Szymczyk, Agnieszka; Czyż, Jarosław; Lech-Marańda, Ewa; Warzocha, Krzysztof; Jamroziak, Krzysztof

2018-05-01

There is limited amount of data available on the comparative efficacy of ibrutinib and idelalisib, the B-cell receptor inhibitors (BCRi) newly approved for relapsed/refractory chronic lymphocytic leukemia/small lymphocytic lymphoma (r/r CLL/SLL) treatment. The aim of our study was to analyze and compare the outcomes of real-world r/r CLL/SLL patients treated with these two BCRi in outside clinical trials. A comparative case matched 1:2 analysis was performed on idelalisib combined with rituximab and ibrutinib efficacy in 102 patients with r/r CLL/SLL from two observational studies of the Polish Adult Leukemia Group (PALG). Both therapies produced similar overall response rates (idelalisib plus rituximab 76.4% and ibrutinib 72.1%). Median progression-free survival (PFS) and overall survival (OS) in both groups were not reached. Furthermore, no significant difference was observed between both BCRi regimens in regard to PFS (HR=0.75, 95% CI=0.30-1.86, p=0.55) and OS (HR=0.65, 95%CI=0.26-1.68, p=0.39). In summary, the results of this retrospective analysis suggest that idelalisib combined with rituximab and ibrutinib therapies have comparable activity in r/r CLL/SLL in daily clinical practice. Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Clinical impact of B-cell depletion with the anti-CD20 antibody rituximab in chronic fatigue syndrome: a preliminary case series

Directory of Open Access Journals (Sweden)

Mella Olav

2009-07-01

Full Text Available Abstract Background Chronic fatigue syndrome (CFS is a disease of unknown aetiology. A patient with CFS had unexpected, marked recovery of CFS symptoms lasting for five months during and after cytotoxic chemotherapy for Hodgkin's disease. We reasoned that the transient CFS recovery was related to methotrexate treatment, which induces immunomodulation in part through B-cell depletion. Methods In a case series, this patient and two additional CFS patients were B-cell depleted by infusion of the monoclonal anti-CD20 antibody rituximab. Results All three had improvement of all CFS symptoms. Patients 1 and 2 had major amelioration from 6 weeks after intervention, patient 3 slight improvement from the same time, but then improved markedly from 26 weeks after intervention. The symptomatic effect lasted until weeks 16, 18 and 44, respectively. At relapse, all were retreated with a single (patient 1 or double rituximab infusion (patients 2 and 3. Again, all three had marked symptom improvement, mimicking their first response. After new symptom recurrence, patients 1 and 2 were given weekly oral methotrexate, patient 1 having effect also from this agent. Patients 1 and 2 were again treated for a third rituximab infusion after new relapse, again with a marked clinical benefit. No unexpected toxicity was seen. Conclusion These observations suggest that B-lymphocytes are involved in CFS pathogenesis for a subset of patients. Benefit for all CFS symptoms, the delayed symptom relief following B-cell depletion, the kinetics of relapses, and the effect also from methotrexate treatment, provide suggestive evidence that B-cells play a significant role in the ongoing clinical features, and that CFS may be amenable to therapeutic interventions aimed at modifying B-cell number and function. More systematic investigations of this therapeutic strategy, and of its biological basis, are now needed.

Rituximab versus cyclophosphamide for the treatment of connective tissue disease-associated interstitial lung disease (RECITAL): study protocol for a randomised controlled trial.

Science.gov (United States)

Saunders, Peter; Tsipouri, Vicky; Keir, Gregory J; Ashby, Deborah; Flather, Marcus D; Parfrey, Helen; Babalis, Daphne; Renzoni, Elisabetta A; Denton, Christopher P; Wells, Athol U; Maher, Toby M

2017-06-15

Interstitial lung disease (ILD) frequently complicates systemic autoimmune disorders resulting in considerable morbidity and mortality. The connective tissue diseases (CTDs) most frequently resulting in ILD include: systemic sclerosis, idiopathic inflammatory myositis (including dermatomyositis, polymyositis and anti-synthetase syndrome) and mixed connective tissue disease. Despite the development, over the last two decades, of a range of biological therapies which have resulted in significant improvements in the treatment of the systemic manifestations of CTD, the management of CTD-associated ILD has changed little. At present there are no approved therapies for CTD-ILD. Following trials in scleroderma-ILD, cyclophosphamide is the accepted standard of care for individuals with severe or progressive CTD-related ILD. Observational studies have suggested that the anti-CD20 monoclonal antibody, rituximab, is an effective rescue therapy in the treatment of refractory CTD-ILD. However, before now, there have been no randomised controlled trials assessing the efficacy of rituximab in this treatment population. RECITAL is a UK, multicentre, prospective, randomised, double-blind, double-dummy, controlled trial funded by the Efficacy and Mechanism Evaluation Programme of the Medical Research Council and National Institute for Health Research. The trial will compare rituximab 1 g given intravenously, twice at an interval of 2 weeks, with intravenously administered cyclophosphamide given monthly at a dose of 600 mg/m 2 body surface area in individuals with ILD due to systemic sclerosis, idiopathic inflammatory myositis (including anti-synthetase syndrome) or mixed connective tissue disease. A total of 116 individuals will be randomised 1:1 to each of the two treatment arms, with stratification based on underlying CTD, and will be followed for a total of 48 weeks from first dose. The primary endpoint for the study will be change in forced vital capacity (FVC) at 24�

Higher World Health Organization grades of follicular lymphoma correlate with better outcome in two Nordic Lymphoma Group trials of rituximab without chemotherapy

DEFF Research Database (Denmark)

Wahlin, Björn Engelbrekt; Sundström, Christer; Sander, Birgitta

2014-01-01

Abstract A common treatment for follicular lymphoma is rituximab monotherapy. To identify patients for whom this regimen is adequate as first-line therapy, we applied the World Health Organization (WHO) classification for grading follicular lymphoma in a prospective central pathology review...... increased with the malignant cell size (p useful tool for personalized therapy....

Chemoimmunotherapy for Relapsed/Refractory and Progressive 17p13 Deleted Chronic Lymphocytic Leukemia (CLL) Combining Pentostatin, Alemtuzumab, and Low Dose Rituximab is Effective and Tolerable and Limits Loss of CD20 Expression by Circulating CLL Cells

Science.gov (United States)

Zent, Clive S.; Taylor, Ronald P.; Lindorfer, Margaret A.; Beum, Paul V.; LaPlant, Betsy; Wu, Wenting; Call, Timothy G.; Bowen, Deborah A.; Conte, Michael J.; Frederick, Lori A.; Link, Brian K.; Blackwell, Sue E.; Veeramani, Suresh; Baig, Nisar A.; Viswanatha, David S.; Weiner, George J.; Witzig, Thomas E.

2014-01-01

Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL) patients with purine analogue refractory disease or TP53 dysfunction still have limited treatment options and poor survival. Alemtuzumab containing chemoimmunotherapy regimens can be effective but frequently cause serious infections. We report a phase II trial testing the efficacy and tolerability of a short duration regimen combining pentostatin, alemtuzumab, and low dose high frequency rituximab (PAR) designed to decrease the risk of treatment associated infections and limit loss of CD20 expression by CLL cells. The study enrolled 39 patients with progressive CLL that was either relapsed/refractory (n=36) or previously untreated with 17p13 deletion (17p13-)(n=3). Thirteen (33%) patients had both 17p13- and TP53 mutations predicted to be dysfunctional and eight patients had purine analogue refractory CLL without TP53 dysfunction. Twenty-six (67%) patients completed therapy with only five (13%) patients having treatment limiting toxicity, and no treatment related deaths. Twenty-two (56%) patients responded to treatment with 11 (28%) complete responses (four with incomplete bone marrow recovery). Median progression free survival was 7.2 months, time to next treatment 9.1 months, and overall survival 34.1 months. The majority of deaths (82%) were caused by progressive disease including transformed diffuse large B cell lymphoma (n=6). Correlative studies showed that low dose rituximab activates complement and NK cells without a profound and sustained decrease in expression of CD20 by circulating CLL cells. We conclude that PAR is a tolerable and effective therapy for CLL and that low dose rituximab therapy can activate innate immune cytotoxic mechanisms without substantially decreasing CD20 expression. PMID:24723493

Alisertib added to rituximab and vincristine is synthetic lethal and potentially curative in mice with aggressive DLBCL co-overexpressing MYC and BCL2.

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Daruka Mahadevan

Full Text Available Pearson correlation coefficient for expression analysis of the Lymphoma/Leukemia Molecular Profiling Project (LLMPP demonstrated Aurora A and B are highly correlated with MYC in DLBCL and mantle cell lymphoma (MCL, while both Auroras correlate with BCL2 only in DLBCL. Auroras are up-regulated by MYC dysregulation with associated aneuploidy and resistance to microtubule targeted agents such as vincristine. Myc and Bcl2 are differentially expressed in U-2932, TMD-8, OCI-Ly10 and Granta-519, but only U-2932 cells over-express mutated p53. Alisertib [MLN8237 or M], a highly selective small molecule inhibitor of Aurora A kinase, was synergistic with vincristine [VCR] and rituximab [R] for inhibition of cell proliferation, abrogation of cell cycle checkpoints and enhanced apoptosis versus single agent or doublet therapy. A DLBCL (U-2932 mouse model showed tumor growth inhibition (TGI of ∼ 10-20% (p = 0.001 for M, VCR and M-VCR respectively, while R alone showed ∼ 50% TGI (p = 0.001. M-R and VCR-R led to tumor regression [TR], but relapsed 10 days after discontinuing therapy. In contrast, M-VCR-R demonstrated TR with no relapse >40 days after stopping therapy with a Kaplan-Meier survival of 100%. Genes that are modulated by M-VCR-R (CENP-C, Auroras play a role in centromere-kinetochore function in an attempt to maintain mitosis in the presence of synthetic lethality. Together, our data suggest that the interaction between alisertib plus VCR plus rituximab is synergistic and synthetic lethal in Myc and Bcl-2 co-expressing DLBCL. Alisertib plus vincristine plus rituximab [M-VCR-R] may represent a new strategy for DLBCL therapy.

Alisertib added to rituximab and vincristine is synthetic lethal and potentially curative in mice with aggressive DLBCL co-overexpressing MYC and BCL2.

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Mahadevan, Daruka; Morales, Carla; Cooke, Laurence S; Manziello, Ann; Mount, David W; Persky, Daniel O; Fisher, Richard I; Miller, Thomas P; Qi, Wenqing

2014-01-01

Pearson correlation coefficient for expression analysis of the Lymphoma/Leukemia Molecular Profiling Project (LLMPP) demonstrated Aurora A and B are highly correlated with MYC in DLBCL and mantle cell lymphoma (MCL), while both Auroras correlate with BCL2 only in DLBCL. Auroras are up-regulated by MYC dysregulation with associated aneuploidy and resistance to microtubule targeted agents such as vincristine. Myc and Bcl2 are differentially expressed in U-2932, TMD-8, OCI-Ly10 and Granta-519, but only U-2932 cells over-express mutated p53. Alisertib [MLN8237 or M], a highly selective small molecule inhibitor of Aurora A kinase, was synergistic with vincristine [VCR] and rituximab [R] for inhibition of cell proliferation, abrogation of cell cycle checkpoints and enhanced apoptosis versus single agent or doublet therapy. A DLBCL (U-2932) mouse model showed tumor growth inhibition (TGI) of ∼ 10-20% (p = 0.001) for M, VCR and M-VCR respectively, while R alone showed ∼ 50% TGI (p = 0.001). M-R and VCR-R led to tumor regression [TR], but relapsed 10 days after discontinuing therapy. In contrast, M-VCR-R demonstrated TR with no relapse >40 days after stopping therapy with a Kaplan-Meier survival of 100%. Genes that are modulated by M-VCR-R (CENP-C, Auroras) play a role in centromere-kinetochore function in an attempt to maintain mitosis in the presence of synthetic lethality. Together, our data suggest that the interaction between alisertib plus VCR plus rituximab is synergistic and synthetic lethal in Myc and Bcl-2 co-expressing DLBCL. Alisertib plus vincristine plus rituximab [M-VCR-R] may represent a new strategy for DLBCL therapy.

Effect of intravitreal methotrexate and rituximab on interleukin-10 levels in aqueous humor of treated eyes with vitreoretinal lymphoma.

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Harish Raja

Full Text Available Intraocular cytokines are promising diagnostic biomarkers of vitreoretinal lymphoma. Here, we evaluate the utility of IL-10, IL-6 and IL-10/IL-6 for discriminating lymphoma from uveitis and report the effects of intraocular methotrexate and rituximab on aqueous cytokine levels in eyes with lymphoma. This is a retrospective case series including 10 patients with lymphoma and 7 patients with uveitis. Non-parametric Mann-Whitney analysis was performed to determine statistical significance of difference in interleukin levels between lymphoma and uveitis. Compared to eyes with uveitis, eyes with lymphoma had higher levels of IL-10 (U = 7.0; two-tailed p = 0.004 and IL-10/IL-6 (U = 6.0; two-tailed p = 0.003, whereas IL-6 levels were more elevated, although insignificant, in those patients with uveitis than in lymphoma (U = 15.0; two-tailed p = ns. Using a receiver operating characteristic analysis to identify threshold values diagnostic for lymphoma, optimal sensitivity and specificity improved to 80.0% and 100%, respectively, for IL-10>7.025 pg/ml and 90.0% and 100.0%, respectively, for IL-10/IL-6>0.02718. In patients in whom serial interleukin levels were available, regular intravitreal treatment with methotrexate and rituximab was associated with reduction in IL-10 levels over time. In conclusion, optimal IL-10 and IL-10/IL-6 threshold values are associated with a diagnostic sensitivity ≥80% and specificity of 100%. Therefore, these cytokines may serve as a useful adjunct in the diagnosis of lymphoma. While negative IL-10 and IL-10/IL-6 values do not exclude a diagnosis of lymphoma, elevated levels do appear to be consistent with lymphoma clinically. Moreover, elevated levels of IL-10 in the setting of a clinically quiet eye may point to impending disease recurrence. Lastly, once lymphoma is diagnosed, IL-10 levels can be monitored over time to assess disease activity and therapeutic response.

Effect of intravitreal methotrexate and rituximab on interleukin-10 levels in aqueous humor of treated eyes with vitreoretinal lymphoma.

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Raja, Harish; Snyder, Melissa R; Johnston, Patrick B; O'Neill, Brian P; Caraballo, Juline N; Balsanek, Joseph G; Peters, Brian E; Decker, Paul A; Pulido, Jose S

2013-01-01

Intraocular cytokines are promising diagnostic biomarkers of vitreoretinal lymphoma. Here, we evaluate the utility of IL-10, IL-6 and IL-10/IL-6 for discriminating lymphoma from uveitis and report the effects of intraocular methotrexate and rituximab on aqueous cytokine levels in eyes with lymphoma. This is a retrospective case series including 10 patients with lymphoma and 7 patients with uveitis. Non-parametric Mann-Whitney analysis was performed to determine statistical significance of difference in interleukin levels between lymphoma and uveitis. Compared to eyes with uveitis, eyes with lymphoma had higher levels of IL-10 (U = 7.0; two-tailed p = 0.004) and IL-10/IL-6 (U = 6.0; two-tailed p = 0.003), whereas IL-6 levels were more elevated, although insignificant, in those patients with uveitis than in lymphoma (U = 15.0; two-tailed p = ns). Using a receiver operating characteristic analysis to identify threshold values diagnostic for lymphoma, optimal sensitivity and specificity improved to 80.0% and 100%, respectively, for IL-10>7.025 pg/ml and 90.0% and 100.0%, respectively, for IL-10/IL-6>0.02718. In patients in whom serial interleukin levels were available, regular intravitreal treatment with methotrexate and rituximab was associated with reduction in IL-10 levels over time. In conclusion, optimal IL-10 and IL-10/IL-6 threshold values are associated with a diagnostic sensitivity ≥80% and specificity of 100%. Therefore, these cytokines may serve as a useful adjunct in the diagnosis of lymphoma. While negative IL-10 and IL-10/IL-6 values do not exclude a diagnosis of lymphoma, elevated levels do appear to be consistent with lymphoma clinically. Moreover, elevated levels of IL-10 in the setting of a clinically quiet eye may point to impending disease recurrence. Lastly, once lymphoma is diagnosed, IL-10 levels can be monitored over time to assess disease activity and therapeutic response.

ESTUDIO MULTICÉNTRICO LONGITUDINAL DE DEPLECIÓN DE LINFOCITOS B EN LUPUS ERITEMATOSO SISTÉMICO REFRACTARIO: ESTUDIO LESIMAB

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Nieves-Martín, Laura

2014-01-01

Cohorte multicéntrica retrospectiva de pacientes con LES refractario a terapia estándar que fueron tratados con rituximab. Estudio de efectividad y seguridad tras uno o varios cursos de tratamiento. Así mismo análisis lipídico básico de los pacientes antes y después del tratamiento.

MDM2 phenotypic and genotypic profiling, respective to TP53 genetic status, in diffuse large B-cell lymphoma patients treated with rituximab-CHOP immunochemotherapy

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Xu-Monette, Zijun Y; Møller, Michael B; Tzankov, Alexander

2013-01-01

MDM2 is a key negative regulator of the tumor suppressor p53, however, the prognostic significance of MDM2 overexpression in diffuse large B-cell lymphoma (DLBCL) has not been defined convincingly. In a p53 genetically-defined large cohort of de novo DLBCL patients treated with rituximab, cycloph...

An inflammation-based cumulative prognostic score system in patients with diffuse large B cell lymphoma in rituximab era.

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Sun, Feifei; Zhu, Jia; Lu, Suying; Zhen, Zijun; Wang, Juan; Huang, Junting; Ding, Zonghui; Zeng, Musheng; Sun, Xiaofei

2018-01-02

Systemic inflammatory parameters are associated with poor outcomes in malignant patients. Several inflammation-based cumulative prognostic score systems were established for various solid tumors. However, there is few inflammation based cumulative prognostic score system for patients with diffuse large B cell lymphoma (DLBCL). We retrospectively reviewed 564 adult DLBCL patients who had received rituximab, cyclophosphamide, doxorubicin, vincristine and prednisolone (R-CHOP) therapy between Nov 1 2006 and Dec 30 2013 and assessed the prognostic significance of six systemic inflammatory parameters evaluated in previous studies by univariate and multivariate analysis:C-reactive protein(CRP), albumin levels, the lymphocyte-monocyte ratio (LMR), the neutrophil-lymphocyte ratio(NLR), the platelet-lymphocyte ratio(PLR)and fibrinogen levels. Multivariate analysis identified CRP, albumin levels and the LMR are three independent prognostic parameters for overall survival (OS). Based on these three factors, we constructed a novel inflammation-based cumulative prognostic score (ICPS) system. Four risk groups were formed: group ICPS = 0, ICPS = 1, ICPS = 2 and ICPS = 3. Advanced multivariate analysis indicated that the ICPS model is a prognostic score system independent of International Prognostic Index (IPI) for both progression-free survival (PFS) (p systemic inflammatory status was associated with clinical outcomes of patients with DLBCL in rituximab era. The ICPS model was shown to classify risk groups more accurately than any single inflammatory prognostic parameters. These findings may be useful for identifying candidates for further inflammation-related mechanism research or novel anti-inflammation target therapies.

Multicenter Retrospective Analysis of the Effectiveness and Safety of Rituximab in Korean Patients with Refractory Systemic Lupus Erythematosus

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So-Young Bang

2012-01-01

Full Text Available Objective. Although two recent randomized placebo-controlled trials of rituximab (RTX failed to demonstrate efficacy in systemic lupus erythematosus (SLE, clinicians continue to use off-label RTX for cases refractory to current treatments. We evaluated the effectiveness and safety of rituximab for patients with refractory SLE in Korea. Methods. We retrospectively analyzed multicenter patients treated with RTX in Korea. Results. 39 SLE patients treated with RTX were included in the following manner: lupus nephritis 43.6%, hematologic 33.3%, arthritis 7.8%, myositis 7.8%, and others 7.7%. All patients had responded poorly to at least one conventional immunosuppressive agent (mean 2.5 ± 1.1, cyclophosphamide 43.6%, mycophenolate mofetil 48.7%, and other drugs before RTX. Clinical improvements (complete or partial remission occurred in patients with renal disease, hematologic disease, arthritis, myositis, and other manifestations at 6 months after RTX. The SLEDAI score was significantly decreased from 10.8±7.1 at baseline to 6.7±4.0 at 6 months, 6.2±4.1 at 12 months, and 5.5±3.6 at 24 months after RTX (P<0.05. Among 28 clinical responders, 4 patients experienced a relapse of disease at 25±4 months. Infections were noted in 3 patients (7.7%. Conclusion. RTX could be an effective and relatively safe therapeutic option in patients with severe refractory SLE until novel B-cell depletion therapy is available.

Analysis of anti-HLA antibodies in sensitized kidney transplant candidates subjected to desensitization with intravenous immunoglobulin and rituximab.

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Lobashevsky, Andrew L; Higgins, Nancy G; Rosner, Kevin M; Mujtaba, Muhammad A; Goggins, William C; Taber, Tim E

2013-07-27

Preexisting donor-specific antibodies against human leukocyte antigens are major risk factors for acute antibody-mediated and chronic rejection of kidney transplant grafts. Immunomodulation (desensitization) protocols may reduce antibody concentration and improve the success of transplant. We investigated the effect of desensitization with intravenous immunoglobulin and rituximab on the antibody profile in highly sensitized kidney transplant candidates. In 31 transplant candidates (calculated panel-reactive antibody [cPRA], 34%-99%), desensitization included intravenous immunoglobulin on days 0 and 30 and a single dose of rituximab on day 15. Anti-human leukocyte antigen antibodies were analyzed before and after desensitization. Reduction of cPRA from 25% to 50% was noted for anti-class I (5 patients, within 20-60 days) and anti-class II (3 patients, within 10-20 days) antibodies. After initial reduction of cPRA, the cPRA increased within 120 days. In 24 patients, decrease in mean fluorescence intensity of antibodies by more than 50% was noted at follow-up, but there was no reduction of cPRA. Rebound occurred in 65% patients for anti-class I antibodies at 350 days and anti-class II antibodies at 101 to 200 days. Probability of rebound effect was higher in patients with mean fluorescence intensity of more than 10,700 before desensitization, anti-class II antibodies, and history of previous transplant. The desensitization protocol had limited efficacy in highly sensitized kidney transplant candidate because of the short period with antibody reduction and high frequency of rebound effect.

Adverse drug reactions after intravenous rituximab infusion are more common in hematologic malignancies than in autoimmune disorders and can be predicted by the combination of few clinical and laboratory parameters: results from a retrospective, multicenter study of 374 patients.

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D'Arena, Giovanni; Simeon, Vittorio; Laurenti, Luca; Cimminiello, Michele; Innocenti, Idanna; Gilio, Michele; Padula, Angela; Vigliotti, Maria Luigia; De Lorenzo, Sonya; Loseto, Giacomo; Passarelli, Anna; Di Minno, Matteo Nicola Dario; Tucci, Marco; De Feo, Vincenzo; D'Auria, Fiorella; Silvestris, Francesco; Di Minno, Giovanni; Musto, Pellegrino

2017-11-01

Rituximab is an effective treatment for CD20 + B-cell malignancies and autoimmune disorders. However, adverse drug reactions (ADRs) may occur after rituximab infusion, causing, in rare cases, its discontinuation. In this multicenter, retrospective study, among 374 patients treated with rituximab i.v., 23.5% experienced ADRs. Mean follow-up was 20.6 months (range 8-135). Overall, ADRs were significantly more frequent in non-Hodgkin lymphomas (NHL) and chronic lymphocytic leukemias (25-35.9%), than in autoimmune diseases (9.4-17.5%) (p < .0001). Grade 3-4 toxicity was observed in eight patients (2.1%), and in four of them (1% of all patients) definitive drug discontinuation was necessary. Interestingly, three groups of patients with different risk of developing ADR were identified, according to a predictive heat-map developed combining four parameters (splenomegaly, history of allergy, hemoglobin levels and gender) selected by multivariate analysis. This model may be useful in identifying patients at higher risk of ADRs, needing appropriate preventing therapies.

Predictors of Local Recurrence After Rituximab-Based Chemotherapy Alone in Stage III and IV Diffuse Large B-Cell Lymphoma: Guiding Decisions for Consolidative Radiation

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Jegadeesh, Naresh; Rajpara, Raj; Esiashvili, Natia; Shi, Zheng [Department of Radiation Oncology, Emory University, Atlanta, Georgia (United States); Winship Cancer Institute, Emory University, Atlanta, Georgia (United States); Liu, Yuan [Winship Cancer Institute, Emory University, Atlanta, Georgia (United States); Department of Biostatistics and Bioinformatics Shared Resource, Emory University, Atlanta, Georgia (United States); Okwan-Duodu, Derrick [Department of Radiation Oncology, Emory University, Atlanta, Georgia (United States); Winship Cancer Institute, Emory University, Atlanta, Georgia (United States); Flowers, Christopher R. [Winship Cancer Institute, Emory University, Atlanta, Georgia (United States); Department of Medical Oncology, Emory University, Atlanta, Georgia (United States); Khan, Mohammad K., E-mail: drkhurram2000@gmail.com [Department of Radiation Oncology, Emory University, Atlanta, Georgia (United States); Winship Cancer Institute, Emory University, Atlanta, Georgia (United States)

2015-05-01

Purpose: The role of consolidative radiation therapy (RT) for stage III and IV diffuse large B-cell lymphoma (DLBCL) in the era of rituximab is not well defined. There is evidence that some patients with bulky disease may benefit, but patient selection criteria are not well established. We sought to identify a subset of patients who experienced a high local failure rate after receiving rituximab-based chemotherapy alone and hence may benefit from the addition of consolidative RT. Methods and Materials: Two hundred eleven patients with stage III and IV DLBCL treated between August 1999 and January 2012 were reviewed. Of these, 89 had a complete response to systemic therapy including rituximab and received no initial RT. Kaplan-Meier analysis and Cox proportional hazards regression were performed, with local recurrence (LR) as the primary outcome. Results: The median follow-up time was 43.9 months. Fifty percent of patients experienced LR at 5 years. In multivariate analysis, tumor ≥5 cm and stage III disease were associated with increased risk of LR. The 5-year LR-free survival was 47.4% for patients with ≥5-cm lesions versus 74.7% for patients with <5-cm lesions (P=.01). In patients with <5-cm tumors, the maximum standardized uptake value (SUVmax) was ≥15 in all patients with LR. The 5-year LR-free survival was 100% in SUV<15 versus 68.8% in SUV≥15 (P=.10). Conclusions: Advanced-stage DLBCL patients with stage III disease or with disease ≥5 cm appear to be at an increased risk for LR. Patients with <5-cm disease and SUVmax ≥15 may be at higher risk for LR. These patients may benefit from consolidative RT after chemoimmunotherapy.

Predictors of Local Recurrence After Rituximab-Based Chemotherapy Alone in Stage III and IV Diffuse Large B-Cell Lymphoma: Guiding Decisions for Consolidative Radiation

International Nuclear Information System (INIS)

Jegadeesh, Naresh; Rajpara, Raj; Esiashvili, Natia; Shi, Zheng; Liu, Yuan; Okwan-Duodu, Derrick; Flowers, Christopher R.; Khan, Mohammad K.

2015-01-01

Purpose: The role of consolidative radiation therapy (RT) for stage III and IV diffuse large B-cell lymphoma (DLBCL) in the era of rituximab is not well defined. There is evidence that some patients with bulky disease may benefit, but patient selection criteria are not well established. We sought to identify a subset of patients who experienced a high local failure rate after receiving rituximab-based chemotherapy alone and hence may benefit from the addition of consolidative RT. Methods and Materials: Two hundred eleven patients with stage III and IV DLBCL treated between August 1999 and January 2012 were reviewed. Of these, 89 had a complete response to systemic therapy including rituximab and received no initial RT. Kaplan-Meier analysis and Cox proportional hazards regression were performed, with local recurrence (LR) as the primary outcome. Results: The median follow-up time was 43.9 months. Fifty percent of patients experienced LR at 5 years. In multivariate analysis, tumor ≥5 cm and stage III disease were associated with increased risk of LR. The 5-year LR-free survival was 47.4% for patients with ≥5-cm lesions versus 74.7% for patients with <5-cm lesions (P=.01). In patients with <5-cm tumors, the maximum standardized uptake value (SUVmax) was ≥15 in all patients with LR. The 5-year LR-free survival was 100% in SUV<15 versus 68.8% in SUV≥15 (P=.10). Conclusions: Advanced-stage DLBCL patients with stage III disease or with disease ≥5 cm appear to be at an increased risk for LR. Patients with <5-cm disease and SUVmax ≥15 may be at higher risk for LR. These patients may benefit from consolidative RT after chemoimmunotherapy

Rituximab for the treatment of refractory simultaneous anti-glomerular basement membrane (anti-GBM) and membranous nephropathy.

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Bandak, Ghassan; Jones, Bruce A; Li, Jian; Yee, Jerry; Umanath, Kausik

2014-02-01

Antibody-mediated anti-glomerular basement membrane (anti-GBM) disease occurs rarely in the presence of another B-cell disorder, membranous nephropathy. The coexistence of these two autoimmune disorders would be anticipated to require differing, specific therapies targeted to each disease process. We describe a case of concomitant membranous nephropathy and anti-GBM disease in which conventional therapy, including steroids, plasmapheresis and cyclophosphamide, failed to attenuate the anti-GBM disease, yet responded to an alternative treatment of rituximab. This B-cell directed, monoclonal, chimeric antibody treatment substantially reduced anti-GBM antibody titers and led to discontinuation of plasmapheresis, while maintaining the remission of membranous nephropathy and anti-GBM disease.

Procedimiento para hemorroides con prolapso de mucosa: técnica de Longo. Reporte preliminar

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Luis Augusto Borda Mederos

2009-10-01

Full Text Available La hemorroidectomía es una excelente técnica para el tratamiento de las hemorroides grado III y IV pero va asociada invariablemente a dolor postoperatorio. La mucosectomía con stapler circular- procedimiento para prolapso y hemorroides- (PPH ha demostrado menor dolor y recuperación más rápida. No se ha encontrado reportes de la técnica en nuestro país. Objetivo: Evaluar la eficacia y seguridad del PPH en pacientes portadores de hemorroides grado III y IV con prolapso de mucosa rectal. Material y método: Estudio retrospectivo tipo serie de casos de pacientes operados de hemorroides grado III - IV con prolapso de mucosa rectal, entre diciembre de 1998 hasta diciembre 2007 en el Hospital de Emergencias Grau - EsSalud, Hospital G. Almenara I. - EsSalud y Clínica San Borja. Resultados: Se estudiaron 18 pacientes (13 hombres, 5 mujeres. La hospitalización promedio fue de 1,2 días. El tiempo operatorio promedio fue de 17,5 minutos. El 94,4% de los pacientes no refirió dolor o éste fue leve. Un paciente presentó sangrado postoperatorio importante a nivel de la línea de grapas que prolongó su hospitalización, una paciente presentó dolor intenso y una paciente presentó una fístula rectovaginal. Conclusiones: La técnica de PPH es efectiva para tratar la sintomatología de las hemorroides grado III y IV con prolapso mucoso a corto y mediano plazo.(Rev Med Hered 2009;20:190-194.

Vorinostat, a histone deacetylase (HDAC) inhibitor, promotes cell cycle arrest and re-sensitizes rituximab- and chemo-resistant lymphoma cells to chemotherapy agents.

Science.gov (United States)

Xue, Kai; Gu, Juan J; Zhang, Qunling; Mavis, Cory; Hernandez-Ilizaliturri, Francisco J; Czuczman, Myron S; Guo, Ye

2016-02-01

Preclinical models of chemotherapy resistance and clinical observations derived from the prospective multicenter phase III collaborative trial in relapsed aggressive lymphoma (CORAL) study demonstrated that primary refractory/relapsed B cell diffuse large B cell lymphoma has a poor clinical outcome with current available second-line treatments. Preclinically, we found that rituximab resistance is associated with a deregulation on the mitochondrial potential rendering lymphoma cells resistant to chemotherapy-induced apoptotic stimuli. There is a dire need to develop agents capable to execute alternative pathways of cell death in an attempt to overcome chemotherapy resistance. Posttranscriptional histone modification plays an important role in regulating gene transcription and is altered by histone acetyltransferases (HATs) and histone deacetylases (HDACs). HDACs regulate several key cellular functions, including cell proliferation, cell cycle, apoptosis, angiogenesis, migration, antigen presentation, and/or immune regulation. Given their influence in multiple regulatory pathways, HDAC inhibition is an attractive strategy to evaluate its anti-proliferation activity in cancer cells. To this end, we studied the anti-proliferation activity and mechanisms of action of suberoylanilide hydroxamic acid (SAHA, vorinostat) in rituximab-chemotherapy-resistant preclinical models. A panel of rituximab-chemotherapy-sensitive (RSCL) and rituximab-chemotherapy-resistant cell lines (RRCL) and primary tumor cells isolated from relapsed/refractory B cell lymphoma patients were exposed to escalating doses of vorinostat. Changes in mitochondrial potential, ATP synthesis, and cell cycle distribution were determined by Alamar blue reduction, Titer-Glo luminescent assays, and flow cytometric, respectively. Protein lysates were isolated from vorinostat-exposed cells, and changes in members of Bcl-2 family, cell cycle regulatory proteins, and the acetylation status of histone H3 were

Síndrome serotoninérgico en anciano con falla renal crónica tratada con linezolid: reporte de caso

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Mauricio Montoya Cañón

2016-04-01

Entre los factores de riesgo para desarrollo de síndrome serotoninérgico se encuentra el uso de linezolid, que en combinación de otros medicamentos con acción serotoninérgica —como los inhibidores selectivos de recaptación de serotonina, el litio, la trazodona, entre otros— se asocia con la presentación de este cuadro. El síndrome serotoninérgico puede ser evitado con una buena educación al personal médico y la modificación de las conductas de prescripción de medicamentos; el pilar del tratamiento se basa en la suspensión de los fármacos que están causando el cuadro y el planteamiento de medidas de soporte.

A Case Report of Nongerminal Center B-Cell Type Diffuse Large B-Cell Lymphoma Treated to Complete Response with Rituximab and Ibrutinib

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Geoffrey Shouse

2018-01-01

Full Text Available Diffuse large B-cell lymphoma (DLBCL is a molecularly heterogeneous disease consisting of different subtypes with varying clinical behaviors. For example, the activated B-cell-like (ABC type of DLBCL has lower cure rates with traditional chemotherapy regimens. The molecular pathway promoting tumorigenic growth of the ABC type includes a dependence on intracellular signaling by Bruton’s agammaglobulinemia tyrosine kinase (BTK. This specific pathway has led to the investigation of the utility of ibrutinib in treatment of this type of lymphoma at relapse or in combination with standard chemotherapy. In elderly patients stricken with this disease, standard combination chemotherapy can pose significant toxicity. Some reduced intensity regimens have activity but significantly less favorable long-term outcomes and still pose significant toxicity to elderly patients. In the following case, we demonstrate induction of complete response in an elderly patient with significant comorbidities with nongerminal center B-cell type (NGCB DLBCL treated with rituximab, ibrutinib, and prednisone. Toxicity included atrial fibrillation that ultimately led to heart failure as well as sepsis which ultimately led to the patient’s demise. Despite this fact, the response to treatment appeared durable. This case illustrates the utility and limitations of molecularly targeted therapies to treat aggressive lymphoma in frail elderly patients.

Bendamustine mitoxantrone and rituximab (BMR): a new effective regimen for refractory or relapsed indolent lymphomas.

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Weide, Rudolf; Heymanns, Jochen; Gores, Annette; Köppler, Hubert

2002-02-01

Bendamustine (B) and mitoxantrone (M) have been shown to be potent cytotoxic drugs for the treatment of relapsed or refractory indolent lymphomas. The anti-CD20 monoclonal antibody rituximab (R) has produced an overall response rate (ORR) of 50% as a single agent in relapsed or refractory indolent lymphomas. We posed the question whether a combination of the above agents (BMR) could improve these results. This study was an open label, single center pilot study for patients with relapsed or refractory, CD20-positive (indolent) lymphoma or chronic lymphocytic leukaemia. The therapy consisted of bendamustine (80 mg/m2, day 1-3), mitoxantrone (10 mg/m2, day 1), rituximab (375 mg/m2, week 2-5). BM was repeated on day 36 or when the haematological parameters had recovered. The maximum therapy consisted of one BMR-cycle, followed by five BM courses. Treatment was stopped when the disease responded with PR/CR. During March 1999 and December 2000, 20 patients received the BMR-regimen (four secondary high grade lymphoma, 12 indolent lymphoma, four B-CLL). The median age of the patients was 67 years (range 36-82) and their performance status ranged from 0 to 3. Median number of previous treatment regimens was two (1-6). Of the lymphoma patients, 14 had stage IV disease, 1 stage III and 1 stage II. B-CLL patients were all Rai stage IV (Binet C). Overall response rate was 95% (19/20) with seven patients achieving a CR (35%) and 12 patients achieving a PR (60%). Median time to progression is 7 months (1-21) with a median observation time of 7 months (1-21). Response is still durable in 15/20 patients (75%) (1+ to 21+ months after therapy). Symptomatic, reversible grade three or four haematotoxicity occurred in 4/20 patients (20%). Non-symptomatic grade three or four haematotoxicity was seen in 9/20 patients (45%). No major non-haematological toxicity was observed. In conclusion, BMR is a well tolerated, very effective outpatient regimen of treatment for relapsed and refractory

Controversies on Rituximab Therapy in Sjögren Syndrome-Associated Lymphoproliferation

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Luca Quartuccio

2009-01-01

Full Text Available Sjögren's syndrome (SS is a systemic autoimmune disease characterized by chronic inflammation of salivary and lachrymal glands, and frequently accompanied by systemic symptoms. A subgroup of SS patients develops malignant B cell non-Hodgkin's lymphoma (NHL, usually of the mucosa-associated lymphoid tissue (MALT type and very often located in the major salivary glands. Currently, there is a lack of evidence-based intervention therapy which may influence SS-related chronic inflammation and lymphoproliferation. B cells are involved in the pathogenesis of SS, and B cell downregulation may lead to a decrease of disease activity. Rituximab (RTX, a chimeric monoclonal antibody targeting the CD20 antigen on the B cell surface, has been successfully investigated in other autoimmune diseases, such as rheumatoid arthritis, systemic lupus erythematosus, ANCA-associated vasculitis, and mixed cryoglobulinemic syndrome. Preliminary experiences of RTX therapy in SS patients with or without a lymphoproliferative disorder suggest that SS patients with more residual exocrine gland function might better benefit from RTX. Efficacy of RTX in SS-associated B-cell lymphoma, mainly in low-grade salivary gland lymphomas, remains an open issue.

A phase I/II trial to evaluate the safety, feasibility and activity of salvage therapy consisting of the mTOR inhibitor Temsirolimus added to standard therapy of Rituximab and DHAP for the treatment of patients with relapsed or refractory diffuse large cell B-Cell lymphoma – the STORM trial

International Nuclear Information System (INIS)

Witzens-Harig, Mathias; Memmer, Marie Luise; Dreyling, Martin; Hess, Georg

2013-01-01

The current standard treatment of patients with relapsed or refractory diffuse large cell B-Cell lymphoma (DLBCL) primarily consists of intensified salvage therapy and, if the disease is chemo-sensitive, high dose therapy followed with autologous stem cell transplantation. In the rituximab era however, this treatment approach has shown only limited benefit. In particular, patients relapsing after rituximab-containing primary treatment have an adverse prognosis, especially if this occurs within the first year after therapy or if the disease is primarily refractory. Therefore there is an ultimate need for improved salvage treatment approaches. The STORM study is a prospective, multicentre phase I/II study to evaluate the safety, feasibility and activity of salvage therapy consisting of the mTOR inhibitor temsirolimus added to the standard therapy rituximab and DHAP for the treatment of patients with relapsed or refractory DLBCL. The primary objective of the phase I of the trial is to establish the maximum tolerated dose (MTD) of temsirolimus in combination with rituximab and DHAP. The secondary objective is to demonstrate that stem cells can be mobilized during this regimen in patients scheduled to proceed to high dose therapy. In phase II, the previously established maximum tolerated dose of temsirolimus will be used. The primary objective is to evaluate the overall response rate (ORR) in patients with relapsed DLBCL. The secondary objective is to evaluate progression free survival (PFS), overall survival (OS) and toxicity. The study will be accompanied by an analysis of lymphoma subtypes determined by gene expression analysis (GEP). The STORM trial evaluates the safety, feasibility and activity of salvage therapy consisting of the mTOR inhibitor temsirolimus added to standard therapy of rituximab and DHAP for the treatment of patients with relapsed or refractory DLBCL. It also might identify predictive markers for this treatment modality. ClinicalTrials.gov http

CHLORAMBUCIL PLUS RITUXIMAB AS FRONT-LINE THERAPY IN ELDERLY/UNFIT PATIENTS AFFECTED BY B-CELL CHRONIC LYMPHOCYTIC LEUKEMIA: RESULTS OF A SINGLE-CENTRE EXPERIENCE.

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Luca Laurenti

2013-05-01

Full Text Available Currently standard first line therapy for fit patients with B-CLL/SLL are fludarabine-based regimens. Elderly patients or patients with comorbidities poorly tolerate purine analogue-based chemotherapy and they are often treated with Chlorambucil (Chl. However, complete response (CR and overall response (OR rates with Chl are relatively low. We now investigated whether the addition of Rituximab to Chl will improve the efficacy without impairing the tolerability in elderly and unfit patients. We included in our study 27 elderly or unfit patients that had not received prior therapy. All patients were treated with Chl (1mg/Kg per 28-day cycle for 8 cycles plus Rituximab (375 mg/m2 for the first course and 500 mg/m2 for subsequent cycles until the 6th cycle. We obtained an OR rate of 74%. The most frequent adverse effect was grade 3-4 neutropenia, which occurred in 18.5% of the patients. Infections or grade 3-4 extra-hematological side effects were not recorded. None of the patients required reduction of dose, delay of therapy or hospitalization. Overall, these data suggest that Chl-R is an effective and well tolerated regimen in elderly/unfit patients with CLL.

Rituximab administration within 6 months of T cell-depleted allogeneic SCT is associated with prolonged life-threatening cytopenias.

Science.gov (United States)

McIver, Zachariah; Stephens, Nicole; Grim, Andrew; Barrett, A John

2010-11-01

The monoclonal anti-CD20 antibody Rituximab (RTX) is increasingly used in allogeneic stem cell transplantation (SCT) to treat lymphoproliferative disorders and chronic graft-versus-host disease (GVHD). RTX administration can be complicated by delayed and prolonged neutropenia, but the mechanism is unclear. We report the occurrence of profound cytopenias following RTX given in the conditioning regimen or early after T cell-deplete SCT to treat B cell lymphoproliferative disorders or chronic GVHD (cGVHD). Between 2006 and 2009, 102 patients (median age: 43 years, range: 13-68 years), received a myeloablative matched-sibling T cell-deplete SCT for lymphoid or myeloid hematologic disorders. Neutropenia occurring within 4 weeks of treatment developed in 16 of 17 patients given RTX within the first 190 days after SCT. Fourteen patients developed severe neutropenia (count SCT compared to patients with cGVHD not treated with early RTX (P SCT experienced only moderate neutropenia 3 to 5 months after treatment lasting 10 to 20 days while maintaining absolute neutrophil count (ANC) >1.0 × 10⁹/L. Although RTX rapidly controlled cGVHD, we conclude that its administration early after T cell-deplete SCT is associated with prolonged profound and life-threatening cytopenias, and should be avoided. Published by Elsevier Inc.

Combination therapy with rituximab, low-dose cyclophosphamide, and prednisone for idiopathic membranous nephropathy: a case series.

Science.gov (United States)

Cortazar, Frank B; Leaf, David E; Owens, Charles T; Laliberte, Karen; Pendergraft, William F; Niles, John L

2017-02-01

Membranous nephropathy is a common cause of the nephrotic syndrome. Treatment with standard regimens fails to induce complete remission in most patients. We evaluated the efficacy of combination therapy with rituximab, low-dose, oral cyclophosphamide, and an accelerated prednisone taper (RCP) for the treatment of idiopathic membranous nephropathy. We analyzed 15 consecutive patients with idiopathic membranous nephropathy treated with RCP at Massachusetts General Hospital. Seven patients (47%) received RCP as initial therapy, and the other eight patients (53%) received RCP for relapsing or refractory disease. All patients had at least 1 year of follow-up. The co-primary outcomes were attainment of partial and complete remission. Partial remission was defined as a urinary protein to creatinine ratio (UPCR) RCP resulted in high rates of complete remission. Larger studies evaluating this regimen are warranted.

preescolares desnutridos con madres con obesidad y sin obesidad

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Viridiana Vanessa Conzuelo-González

2009-01-01

Full Text Available El primer objetivo fue conocer cuántos menores de cinco años con diferentes grados de desnutrición tienen una madre con sobrepeso/obesidad/ en una comunidad indígena que vive en extrema pobreza y bajo condiciones de migración masculina internacional. El segundo fue comparar tres variables socionutricionales (ingreso familiar, educación de la madre y adecuación nutrimental de la dieta diaria entre estos hogares y los hogares con desnutrición infantil y madres sin obesidad. Se realizó un estudio transversal (2006-2007, en la comunidad mazahua de San Francisco Tepeolulco, Municipio de Temascalcingo; que incluyó a 85 hogares integrados por preescolares con desnutrición inscritos al programa Oportunidades. Se determinó el estado nutrición de los preescolares con indicadores antropométricos y se obtuvo el IMC de las madres de estos infantes. Se aplicó una encuesta socionutricional, incluida el recordatorio de 24 horas, y complementado con la observación participante (cualitativa. Se encontró que 83% de las madres mazahuas presentaron sobrepeso u obesidad. El estado de nutrición de los preescolares con madres con obesidad presentó un porcentaje mayor de desnutrición (76%. En la variable género, se encontró que 54% de los niños con madres con obesidad tenía baja talla. Al relacionar el nivel educativo de la madre, esta variable resultó ser estadísticamente significativa (p=0.015, donde el analfabetismo está más relacionado con la desnutrición infantil que tienen madres de bajo y/o peso normal. La elevada prevalencia de hogares conformados con preescolares con desnutrición y madres con obesidad, es un síntoma más de la pobreza en zonas indígenas en México, con bajo índice de desarrollo humano.

RoboCon: A general purpose telerobotic control center

Energy Technology Data Exchange (ETDEWEB)

Draper, J.V.; Noakes, M.W. [Oak Ridge National Lab., TN (United States). Robotics and Process Systems Div.; Schempf, H. [Carnegie Mellon Univ., Pittsburgh, PA (United States); Blair, L.M. [Human Machine Interfaces, Inc., Knoxville, TN (United States)

1997-02-01

This report describes human factors issues involved in the design of RoboCon, a multi-purpose control center for use in US Department of Energy remote handling applications. RoboCon is intended to be a flexible, modular control center capable of supporting a wide variety of robotic devices.

RoboCon: A general purpose telerobotic control center

International Nuclear Information System (INIS)

Draper, J.V.; Noakes, M.W.; Blair, L.M.

1997-01-01

This report describes human factors issues involved in the design of RoboCon, a multi-purpose control center for use in US Department of Energy remote handling applications. RoboCon is intended to be a flexible, modular control center capable of supporting a wide variety of robotic devices

Tratamiento con estatinas en pacientes pediátricos con síndrome nefrótico resistente a esteroides. Reporte de dos casos

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C Sánchez-García

2017-01-01

Full Text Available El síndrome nefrótico se define por la asociación de proteinuria, hipoalbuminemia, hiperlipidemia y edema. El 80% de los pacientes pediátricos con síndrome nefrótico primario responde a la terapia con esteroides; el 20% restante requiere asociar otros medicamentos para alcanzar la remisión (ciclofosfamida, ciclosporina. La hiperlipidemia en el síndrome nefrótico es debida tanto a un incremento en la síntesis acompañada de disminución en la eliminación de los lípidos de la sangre; siendo la causa directa de esto la proteinuria. La hiperlipidemia incrementa el riesgo cardiovascular, así como el daño glomerular. Con base en esto, la hiperlipidemia persistente en el síndrome nefrótico resistente a esteroides debe ser tratada. Los inhibidores de la 3-hidroxi-3-metilglutaril-coenzima A (HMG-CoA reductasa han demostrado efecto antiinflamatorio, inmunomodulador y antiproliferativo. Por ello el papel de las estatinas en el síndrome nefrótico va más allá de su efecto hipolipemiante. Presentamos dos casos de pacientes pediátricos con diagnóstico de síndrome nefrótico resistente a esteroides y su evolución durante el tratamiento con ciclosporina y estatinas.

Monitorización con potenciales evocados somatosensoriales durante la descompresión occipitocervical en un lactante con acondroplasia: reporte de un caso

Directory of Open Access Journals (Sweden)

Diva Paola Ospino Arévalo

2005-02-01

Full Text Available Se revisa el caso de un paciente de ocho meses de edad, con acondroplasia y síntomas sugestivos de compresión cervicomedular. Los síntomas incluían convulsiones tónico-clónicas generalizadas, irritabilidad, episodios frecuentes de apnea, control cefálico nulo, flacidez generalizada, reflejos osteotendinosos abolidos y fontanela abombada. Los estudios radiológicos incluyeron tomografía computarizada (TC y resonancia magnética (RM que mostraron la compresión, y signos de mielopatía cervical crónica, esto último fue confirmado con estudio de potenciales evocados somatosensoriales (PESS preoperatorios del nervio mediano. Al paciente se le hicieron descompresión de la fosa posterior y laminectomía de C-1. La monitorización con PESS intraoperatorios continuos se usó para observar los cambios electrofisiológicos que se pueden presentar con la descompresión medular, y además para ayudar a determinar la extensión de la descompresión requerida.

Highest clinical effectiveness of rituximab in autoantibody-positive patients with rheumatoid arthritis and in those for whom no more than one previous TNF antagonist has failed: pooled data from 10 European registries

NARCIS (Netherlands)

Chatzidionysiou, K.; Lie, E.; Nasonov, E.; Lukina, G.; Hetland, M.L.; Tarp, U.; Gabay, C.; Riel, P.L. van; Nordstrom, D.C.; Gomez-Reino, J.; Pavelka, K.; Tomsic, M.; Kvien, T.K.; Vollenhoven, R.F. van

2011-01-01

OBJECTIVE: To assess the 6-month effectiveness of the first rituximab (RTX) course in rheumatoid arthritis (RA) and to identify possible predictors of response. METHOD: 10 European registries submitted anonymised datasets (baseline, 3- and 6-month follow-up) from patients with RA who had started

Ivermectin-related adverse clinical events in patients treated for Mansonella ozzardi infections Efectos clínicos adversos relacionados con ivermectina en pacientes tratados por infecciones con Mansonella ozzarddi

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Alejandro J. Krolewiecki

2011-03-01

Full Text Available We report the occurrence of serious reactions after treatment with oral ivermectin in two patients with Mansonella ozzardi infections. Both had systemic and respiratory symptoms and recovered without sequelae. Follow-up revealed clearance of microfilaremia in both cases, with relapse in one of them. These reactions are well described in the treatment of other filarial infections, but have not yet been reported in the treatment of M. ozzardi. We are now reporting the first such known reactions with this helminthiasis.Se informa la aparición de reacciones adversas graves con el tratamiento con ivermectina oral en dos pacientes con infección por Mansonella ozzardi. Ambos presentaron síntomas respiratorios y sistémicos y se recuperaron sin secuelas. El seguimiento mostró ausencia de microfilaremia en ambos casos, con recidiva en uno de ellos. Estas reacciones, bien conocidas durante el tratamiento de otras filariosis, se describen por primera vez con esta helmintiasis.

Mortality in patients with interstitial lung disease treated with rituximab or TNFi as a first biologic.

Science.gov (United States)

Druce, Katie L; Iqbal, Kundan; Watson, Kath D; Symmons, Deborah P M; Hyrich, Kimme L; Kelly, Clive

2017-01-01

Guidelines cautioned prescribing of tumour necrosis factor inhibitors (TNFi) to patients with rheumatoid arthritis and interstitial lung disease (RA-ILD) after reports of new or worsening of ILD. Less is known about outcomes among patients with RA-ILD who receive rituximab (RTX). This study compares mortality in patients with RA-ILD who received RTX or TNFi as their first biologic. Participants with RA-ILD recruited to the British Society for Rheumatology Biologics Register for RA were included. Death rates were calculated and risk comparisons were made using Cox regression. Causes of death, including the frequency in which ILD was recorded on death certificates were examined. 43 patients on RTX and 309 on TNFi were included. RTX recipients had shorter disease duration and less disability. Death rates were 94.8 (95%CI: 74.4 to 118.7) and 53.0 (22.9 to 104.6) per 1000 person years, respectively. The adjusted mortality risk was halved in the RTX cohort, but the difference was not statistically significant (HR 0.53, 95% CI: 0.26 to 1.10). ILD was the underlying cause of death in 1 of 7 RTX deaths (14%) and 12 of 76 TNFi deaths (16%). Patients with RA-ILD who received RTX had lower mortality rates compared to TNFi. The absence of information on ILD severity or subtype prevents conclusions of which drug represents the best choice in patients with RA-ILD and active arthritis.

Highest clinical effectiveness of rituximab in autoantibody-positive patients with rheumatoid arthritis and in those for whom no more than one previous TNF antagonist has failed : pooled data from 10 European registries

NARCIS (Netherlands)

Chatzidionysiou, Katerina; Lie, Elisabeth; Nasonov, Evgeny; Lukina, Galina; Hetland, Merete Lund; Tarp, Ulrik; Gabay, Cem; van Riel, Piet L. C. M.; Nordstrom, Dan C.; Gomez-Reino, Juan; Pavelka, Karel; Tomsic, Matija; Kvien, Tore K.; van Vollenhoven, Ronald F.

Objective To assess the 6-month effectiveness of the first rituximab (RTX) course in rheumatoid arthritis (RA) and to identify possible predictors of response. Method 10 European registries submitted anonymised datasets (baseline, 3- and 6-month follow-up) from patients with RA who had started RTX,

Absceso hepático por Klebsiella pneumoniae, asociado con bacteriemia y meningitis: Reporte de un caso

OpenAIRE

Yucumá-Gutiérrez, Samuel; Duran-Gutiérrez, Luis F; Osorio-Pinzón, Johanna V; Álzate-Carvajal, Verónica; Mondragón-Cardona, Álvaro

2016-01-01

El absceso hepático, continúa siendo un importante problema de salud pública. El causado por Klebsiella pneumoniae, se ha descrito en un 29% de los casos en algunas series. Con una mortalidad hasta del 11,3%, se presenta con mayor frecuencia en pacientes con diabetes mellitus, relacionándose con complicaciones a distancia, como meningitis, absceso cerebral y afección pulmonar. Se presenta el caso de un hombre sin factores de riesgo, con síndrome de absceso hepático por Klebsiella pneumoniae c...

Safety and activity of ibrutinib plus rituximab for patients with high-risk chronic lymphocytic leukaemia: a single-arm, phase 2 study.

Science.gov (United States)

Burger, Jan A; Keating, Michael J; Wierda, William G; Hartmann, Elena; Hoellenriegel, Julia; Rosin, Nathalie Y; de Weerdt, Iris; Jeyakumar, Ghayathri; Ferrajoli, Alessandra; Cardenas-Turanzas, Marylou; Lerner, Susan; Jorgensen, Jeffrey L; Nogueras-González, Graciela M; Zacharian, Gracy; Huang, Xuelin; Kantarjian, Hagop; Garg, Naveen; Rosenwald, Andreas; O'Brien, Susan

2014-09-01

Ibrutinib, an orally administered covalent inhibitor of Bruton's tyrosine kinase (BTK), is an effective treatment for relapsed chronic lymphocytic leukaemia (CLL). We investigated the activity and safety of the combination of ibrutinib with the monoclonal antibody rituximab in patients with high-risk CLL. In this single-arm phase 2 study, we enrolled adult patients with high-risk CLL at the MD Anderson Cancer Center (Houston, TX, USA). All enrolled participants had high-risk cytogenetic abnormalities (deletion 17p, TP53 mutation, or deletion 11q) or a short progression-free survival (PFS ibrutinib 420 mg together with rituximab (375 mg/m(2), intravenously, every week during cycle 1, then once per cycle until cycle 6), followed by continuous daily single-agent ibrutinib 420 mg until disease progression or until toxicities or complications precluded further treatment. The primary endpoint was progression-free survival in the intention-to-treat population. This study is registered with ClinicalTrials.gov number NCT01520519, and is no longer accruing patients. Between Feb 28, 2012, and Sept 11, 2012, we enrolled 40 patients with CLL with high-risk disease features, 20 of whom had deletion 17p (del[17p]) or TP53 mutations (16 previously treated, four untreated), 13 had relapsed CLL with deletion 11q (del[11q]), and seven a PFS less than 36 months after first-line chemoimmunotherapy. 18-month PFS in all patients was 78·0% (95% CI 60·6-88·5), whereas in those with a del(17p) or TP53 mutation it was 72·4% (45·6-87·6) Toxicity was mainly mild to moderate in severity (grade 1-2). Diarrhoea occurred in ten (25%) patients (grade 1 in nine patients and grade 2 in one), bleeding events in 14 (33%) patients (eight grade 1 and five grade 2), nausea or vomiting in 15 patients (38%) (ten grade 1 and five grade 2), and fatigue in seven (18%) patients (four grade 1 and three grade 2). Five patients (13%) had grade 3 infections (two lung infections, one upper respiratory tract

An attempt to induce transient immunosuppression pre-erythrocytapheresis in a girl with sickle cell disease, a history of severe delayed hemolytic transfusion reactions and need for hip prosthesis

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Alessandro Cattoni

2013-06-01

Full Text Available We report on a case of delayed hemolytic transfusion reaction (DHTR occurred 7 days after an erythrocytapheresis or eritroexchange procedure (EEX treated with rituximab and glucocorticoids in a 15-years old patient with sickle cell disease. EEX was performed despite a previous diagnosis of alloimmunization, in order to reduce hemoglobin S rate before a major surgery for avascular necrosis of the femoral head. A first dose of rituximab was administered before EEX. However, rituximab couldn’t prevent DHTR that occurred with acute hemolysis, hemoglobinuria and hyper-bilirubinemia. A further dose of rituximab and three boli of methylprednisolone were given after the onset of the reaction. It is likely that the combined use of rituximab and steroids managed to gradually improve both patient’s general conditions and hemoglobin levels. Nor early or late side effects were registered in a 33-months follow-up period. This report suggests the potential effectiveness and safety of rituximab in combination with steroids in managing and mitigating the symptoms of delayed post-transfusional hemolytic reactions in alloimmunized patients affected by sickle cell disease with absolute need for erythrocytapheresis.

Disease: H01657 [KEGG MEDICUS

Lifescience Database Archive (English)

Full Text Available standard treatment for SRNS. It has been reported that additional rituximab treatment combined with convent...287] Mizoribine [DR:D01392] Rituximab [DR:D02994] See also H00626 Focal segmental

Dexamethasone, rituximab and cyclophosphamide for relapsed and/or refractory and treatment-naïve patients with Waldenstrom macroglobulinemia.

Science.gov (United States)

Paludo, Jonas; Abeykoon, Jithma P; Kumar, Shaji; Shreders, Amanda; Ailawadhi, Sikander; Gertz, Morie A; Kourelis, Taxiarchis; King, Rebecca L; Reeder, Craig B; Leung, Nelson; Kyle, Robert A; Buadi, Francis K; Habermann, Thomas M; Dingli, David; Witzig, Thomas E; Dispenzieri, Angela; Lacy, Martha Q; Go, Ronald S; Lin, Yi; Gonsalves, Wilson I; Warsame, Rahma; Lust, John A; Rajkumar, S Vincent; Ansell, Stephen M; Kapoor, Prashant

2017-10-01

The management of Waldenström macroglobulinaemia (WM) relies predominantly on small trials, one of which has demonstrated activity of dexamethasone, rituximab and cyclophosphamide (DRC) in the frontline setting. We report on the efficacy of DRC, focusing on relapsed/refractory (R/R) patients. Ibrutinib, a recently approved agent in WM demonstrated limited activity in patients with MYD88 WT genotype. Herein, we additionally report on the activity of DRC based on the MYD88 L265P mutation status. Of 100 WM patients evaluated between January 2007 and December 2014 who received DRC, 50 had R/R WM. The overall response rate (ORR) was 87%. The median progression-free survival (PFS) and time-to-next-therapy (TTNT) were 32 (95% confidence interval [CI]: 15-51) and 50 (95% CI: 35-60) months, respectively. In the previously untreated cohort (n = 50), the ORR was 96%, and the median PFS and TTNT were 34 months (95% CI: 23-not reached [NR]) and NR (95% CI: 37-NR), respectively. Twenty-five (86%) of 29 genotyped patients harbored MYD88 L265P . The response rates and outcomes were independent of MYD88 mutation status. Grade ≥3 adverse effects included neutropenia (20%), thrombocytopenia (7%) and infections (3%). Similar to the frontline setting, DRC is an effective and well-tolerated salvage regimen for WM. In contrast to ibrutinib, DRC offers a less expensive, fixed-duration option, with preliminary data suggesting efficacy independent of the patients' MYD88 status. © 2017 John Wiley & Sons Ltd.

Ibrutinib in combination with rituximab in relapsed or refractory mantle cell lymphoma: a single-centre, open-label, phase 2 trial.

Science.gov (United States)

Wang, Michael L; Lee, Hun; Chuang, Hubert; Wagner-Bartak, Nicolaus; Hagemeister, Frederick; Westin, Jason; Fayad, Luis; Samaniego, Felipe; Turturro, Francesco; Oki, Yasuhiro; Chen, Wendy; Badillo, Maria; Nomie, Krystle; DeLa Rosa, Maria; Zhao, Donglu; Lam, Laura; Addison, Alicia; Zhang, Hui; Young, Ken H; Li, Shaoying; Santos, David; Medeiros, L Jeffrey; Champlin, Richard; Romaguera, Jorge; Zhang, Leo

2016-01-01

Ibrutinib is approved in the EU, USA, and other countries for patients with mantle cell lymphoma who received one previous therapy. In a previous phase 2 study with single-agent ibrutinib, the proportion of patients who achieved an objective response was 68%; 38 (34%) of 111 patients had transient lymphocytosis. We hypothesised that adding rituximab could target mantle cell lymphoma cells associated with redistribution lymphocytosis, leading to more potent antitumour activity. Patients with a confirmed mantle cell lymphoma diagnosis (based on CD20-positive and cyclin D1-positive cells in tissue biopsy specimens), no upper limit on the number of previous treatments received, and an Eastern Cooperative Oncology Group performance status score of 2 or less were enrolled in this single-centre, open-label, phase 2 study. Patients received continuous oral ibrutinib (560 mg) daily until progressive disease or unacceptable toxic effects. Rituximab 375 mg/m(2) was given intravenously once per week for 4 weeks during cycle 1, then on day 1 of cycles 3-8, and thereafter once every other cycle up to 2 years. The primary endpoint was the proportion of patients who achieved an objective response in the intention-to-treat population and safety assessed in the as-treated population. The study is registered with ClinicalTrials.gov, number NCT01880567, and is still ongoing, but no longer accruing patients. Between July 15, 2013, and June 30, 2014, 50 patients were enrolled. Median age was 67 years (range 45-86), and the median number of previous regimens was three (range 1-9). At a median follow-up of 16·5 months (IQR 12·09-19·28), 44 (88%, 95% CI 75·7-95·5) patients achieved an objective response, with 22 (44%, 30·0-58·7) patients achieving a complete response, and 22 (44%, 30·0-58·7) a partial response. The only grade 3 adverse event in >=10% of patients was atrial fibrillation, which was noted in six (12%) patients. Grade 4 diarrhoea and neutropenia occurred in one

Splenic marginal zone lymphoma: excellent outcomes in 64 patients treated in the rituximab era.

Science.gov (United States)

Starr, Adam G; Caimi, Paolo F; Fu, PingFu; Massoud, Mira R; Meyerson, Howard; Hsi, Eric D; Mansur, David B; Cherian, Sheen; Cooper, Brenda W; De Lima, Marcos J G; Lazarus, Hillard M; Gerson, Stanton L; Jagadeesh, Deepa; Smith, Mitchell R; Dean, Robert M; Pohlman, Brad L; Hill, Brian T; William, Basem M

2017-08-01

Splenic marginal zone lymphoma (SMZL) is a rare non-Hodgkin lymphoma. We sought to identify prognostic factors and define outcomes in a cohort of 64 patients with SMZL who were treated at two large academic medical centers in North America in the rituximab era. Over a median follow-up of 37.8 (range 6-167.1) months, Kaplan-Meier estimate of median OS was 156.3 months and median PFS was 52.9 months. On univariate analysis, baseline hemoglobin marginally significant with regard to OS (p = 0.056). Splenectomy was not predictive of OS or PFS (p = 0.563 and 0.937, respectively). Transformation to diffuse large B-cell lymphoma occurred in four (6.3%) patients during the observation period. OS was comparable to contemporaneous cohorts of patients with extranodal and nodal marginal lymphomas and FLIPI score was highly predictive for inferior PFS and OS when all three cohorts were analyzed together. Outcomes of SMZL, in our series, were excellent, with a median OS of >13 years. Low hemoglobin and high-risk FLIPI were associated with inferior outcomes.

Comparative efficacy and safety of tocilizumab, rituximab, abatacept and tofacitinib in patients with active rheumatoid arthritis that inadequately responds to tumor necrosis factor inhibitors: a Bayesian network meta-analysis of randomized controlled trials.

Science.gov (United States)

Lee, Young Ho; Bae, Sang-Cheol

2016-11-01

This study aimed to assess the relative efficacy and safety of biologics and tofacitinib in patients with rheumatoid arthritis (RA) showing an inadequate response to tumor necrosis factor (TNF) inhibitors. We performed a Bayesian network meta-analysis to combine the direct and indirect evidence from randomized controlled trials (RCTs) examining the efficacy and safety of tocilizumab, rituximab, abatacept and tofacitinib in patients with RA that inadequately responds to TNF inhibitors. Four RCTs including 1796 patients met the inclusion criteria. The tocilizumab 8 mg group showed a significantly higher American College of Rheumatology 20% (ACR20) response rate than the abatacept and tofacitinib groups. Ranking probability based on surface under the cumulative ranking curve (SUCRA) indicated that tocilizumab 8 mg had the highest probability of being the best treatment for achieving the ACR20 response rate (SUCRA = 0.9863), followed by rituximab (SUCRA = 0.6623), abatacept (SUCRA = 0.5428), tocilizumab 4 mg (SUCRA = 0.4956), tofacitinib 10 mg (SUCRA = 0.4715), tofacitinib 5 mg (SUCRA = 0.3415) and placebo (SUCRA = 0). In contrast, the safety based on the number of withdrawals due to adverse events did not differ significantly among the treatment options. Tocilizumab 8 mg was the second-line non-TNF biologic with the highest performance regarding an early good response based on ACR20 response rate and acceptable safety profile, followed by rituximab, abatacept and tofacitinib in patients with RA and an inadequate response to anti-TNF therapy, and none of these treatments were associated with a significant risk of withdrawal due to adverse events. © 2015 Asia Pacific League of Associations for Rheumatology and Wiley Publishing Asia Pty Ltd.

ConsExpo - Consumer Exposure and Uptake Models -Program Manual

NARCIS (Netherlands)

Delmaar JE; Park MVDZ; Engelen JGM van; SIR

2006-01-01

This report provides guidance to the use of ConsExpo 4.0, successor to ConsExpo 3.0, a computer program that was developed to assist in the exposure assessment of compounds in non-food consumer products. The wide range of available consumer products is associated with an even wider variation in

Denervación renal percutánea mediante el uso de catéter con balón en pacientes con hipertensión arterial resistente

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Isabel C. Marín-Orozco

2015-11-01

El objetivo del presente reporte es describir detalladamente dos casos de hipertensión arterial resistente, tratados mediante ablación con radiofrecuencia con el nuevo dispositivo Vessix® de la compañía Boston Scientific.

A patient with C protein deficiency and multiple thromboses. case report Paciente con deficiencia de proteína C y múltiples trombosis: reporte de caso

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Alejandro Román González

2007-08-01

Full Text Available Inherited thrombophilias are an important group of diseases that should be taken into account in the study of patients with thromboembolic disease, particularly in those whose clinical presentation includes frequent and recurrent thrombotic episodes at young age, in unusual sites, and a familial history of thrombosis. We report the case of a patient with C protein deficiency which developed deep venous thromboses of both legs when he was 36 and 37 years old. At 51 years of age he suffered from mesenteric thrombosis requiring surgical treatment and small intestine transplantation. His father had deep venous thrombosis. This is the first report of C protein deficiency in the Colombian literature. Other inherited thrombophilias such as the G20210A mutation in the prothrombin gene and actor V Leiden were absent. Se debe considerar un estado de hipercoagulabilidad primaria o trombofilia heredada en los pacientes con enfermedad tromboembólica venosa. La sospecha clínica se debe dirigir a los pacientes con presentación temprana, recurrente, familiar o en sitios anatómicos poco usuales. En este reporte se describe el caso de un paciente con déficit de proteína C de la coagulación, quien desarrolló trombosis venosa profunda del miembro inferior derecho a los 36 años y un año después, trombosis venosa profunda del miembro inferior izquierdo. A la edad de 51 años presentó trombosis de vasos mesentéricos que condujo a una resección intestinal extensa lo que obligó a un trasplante de intestino delgado. Su padre había presentado trombosis venosa de los miembros inferiores. Se descartó la presencia asociada de la mutación G20210A de la protrombina y del Factor V Leiden. Hasta donde sabemos, es el primer caso de deficiencia de proteína C de la coagulación informado en la literatura colombiana.

Caracterización de pacientes con lesiones pigmentarias de piel con riesgo de transformación maligna

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María Elena Izquierdo Izquierdo

2015-06-01

Full Text Available Fundamento: el melanoma es el más terrible y mortífero de los cánceres de piel. Se origina frecuentemente a partir de un nevo melanocítico con riesgo de transformación maligna. Estas lesiones pigmentadas se diagnostican cada vez más en edades tan tempranas como la adolescencia. Objetivo: caracterizar los pacientes en edades pediátricas con signos de lesiones pigmentarias de la piel con riesgo de transformación maligna. Métodos: se realizó un estudio prospectivo de corte transversal en un grupo de 50 pacientes en edades entre 5 y 19 años, que asistieron a la consulta de dermatología del Hospital Pediátrico de Centro Habana en el año 2010, con signos de lesiones pigmentarias de la piel con riesgo de transformación maligna. Se aplicó un instrumento de recogida de datos, con previo consentimiento informado. Se utilizó la estadística descriptiva para el procesamiento de los datos. Resultados: en la población de estudio predominó la adolescencia temprana, el grupo de riesgo con daño actínico crónico y el fototipo III. Estuvo presente el antecedente familiar de cáncer de piel no-melanoma. La lesión más frecuente fue la de nevo melanocítico displásico. Además, se reportó un caso de carcinoma basal en paciente de fototipo II, perteneciente al grupo de riesgo de xeroderma pigmentoso. Conclusiones: se evidenció la transformación maligna de lesiones pigmentarias en piel de pacientes de grupos de riesgo.

The Predictive Value of Interim and Final [18F] Fluorodeoxyglucose Positron Emission Tomography after Rituximab-Chemotherapy in the Treatment of Non-Hodgkin's Lymphoma: A Meta-Analysis

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Yuyuan Zhu

2013-01-01

Full Text Available Background and Purpose. The aim of this study is to determine the prognostic value of interim and final FDG-PET in major histotypes of B-cell NHL patients treated with rituximab containing-chemotherapy. Methods. We searched for articles published in English, limited to lymphoma, rituximab, and FDG-PET, and dedicated to deal with the impact on progression and survival. The log hazard ratios (HR and their variances were estimated. Results. A PubMed and Scopus review of published trials identified 13 studies of Progression-free survival (PFS and overall survival (OS which were set as the main outcome measures. The combined HRs of I-PET for PFS and OS in DLBCL were 4.4 (P=0.11 and 3.99 (P=0.46, respectively. The combined HRs of F-PET for PFS and OS in DLBCL were 5.91 (P=0.39 and 6.75 (P=0.92, respectively. Regarding to non-DLBCL with F-PET, the combined HRs of F-PET for PFS and OS were 4.05 (P=0.79 and 5.1 (P=0.51, respectively. No publication bias existed. Conclusion. In DLBCL, both I-PET and F-PET can be performed for survival and progression analysis. But in other B-cell subtypes such as follicular lymphoma (FL and mantle cell lymphoma (MCL, it would be necessary to perform F-PET for predictive purposes.

Niña con erucismo hemorrágico por Lonomia spp.: reporte de un caso

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Walter Peña-Vásquez

Full Text Available Los accidentes causados por las setas urticantes o venenosas de las orugas de lepidópteros, se conocen como erucismo. Estos accidentes se producen por el contacto accidental, especialmente por los niños, con las cerdas sobre el cuerpo del insecto, conectadas con glándulas venenosas. Los síntomas pueden ser locales o sistémicos, con presentaciones clínicas fatales. El accidente ocasionado por las orugas del género Lonomia spp. puede desencadenar síndromes hemorrágicos, constituyendo estos la forma más grave de erucismo. Se reporta el caso de una niña de 5 años, procedente del poblado de Villarondos, en la Amazonía del Perú, departamento de Huánuco, la cual incidentalmente se hinca con las cerdas de una oruga, cursando luego con anemia hemolítica, plaquetopenia y trastorno de la coagulación. El diagnóstico fue establecido por la anamnesis, cuadro clínico, exámenes de laboratorio y respuesta al suero antilonómico. Se discuten los aspectos clínicos, laboratoriales y terapéuticos de erucismo por Lonomia spp.

Tratamiento con estatinas en pacientes pediátricos con síndrome nefrótico resistente a esteroides. Reporte de dos casos

OpenAIRE

C Sánchez-García; A A Bailón-Ortega; S Zaltzman-Girshevich

2017-01-01

El síndrome nefrótico se define por la asociación de proteinuria, hipoalbuminemia, hiperlipidemia y edema. El 80% de los pacientes pediátricos con síndrome nefrótico primario responde a la terapia con esteroides; el 20% restante requiere asociar otros medicamentos para alcanzar la remisión (ciclofosfamida, ciclosporina). La hiperlipidemia en el síndrome nefrótico es debida tanto a un incremento en la síntesis acompañada de disminución en la eliminación de los lípidos de la sangre; siendo la c...

Rearrangements of MYC gene facilitate risk stratification in diffuse large B-cell lymphoma patients treated with rituximab-CHOP

DEFF Research Database (Denmark)

Tzankov, Alexandar; Xu-Monette, Zijun Y; Gerhard, Marc

2014-01-01

In order to address the debatable prognostic role of MYC rearrangements in diffuse large B-cell lymphoma patients treated with rituximab, cyclophosphamide, hydroxydaunorubicin, vincristine, and prednisone, we evaluated MYC rearrangements by fluorescence in situ hybridization in 563 cases using...... with the dual-fusion probes, 15 detectable only with the break-apart probes and 20 detectable with both dual-fusion probes and break-apart probes. MYC rearrangements correlated with germinal center B-cell origin (P=0.02), MYC protein expression (P=0.032), and larger tumor mass size (P=0.0003). Patients with MYC...... was prognostically additive. Radiotherapy seemed to diminish the prognostic effects of MYC rearrangements in diffuse large B-cell lymphoma patients since only 2/10 irradiated patients with MYC rearrangements died of/with disease, compared with 16/28 non-irradiated patients with MYC rearrangements. We conclude...

Linfoma angioinmunoblástico de células T

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Gargantilla P

2016-09-01

Full Text Available Se trata de un linfoma muy agresivo, con una mediana de supervivencia en torno a los 3 años. En cuanto al tratamiento, se han ensayado varias modalidades terapéuticas entre las cuales se encuentran los corticoides, los fármacos citotóxicos (vorinostat, romidepsin, panbinostat y belinostat y los inmunomoduladores (rituximab, lenalidomide.

MANEJO TERAPÉUTICO DE LA INTOXICACIÓN CON FLUORACETATO DE SODIO (GUAYAQUIL® EN CANINOS: REPORTE DE CINCO CASOS –2012-2013–

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V. M. Molina

2014-01-01

Full Text Available El presente reporte relata el manejo terapéutico de la intoxicación con fluoracetato de sodio dispensado a cinco caninos en la Clínica Veterinaria de Antioquia, Medellín (Co-lombia, entre los años 2012 y 2013. Cinco pacientes caninos llegaron a consulta con cuadro neurológico, disforia y convulsiones, con una hora de evolución. Los animales entraron en contacto con el fluoracetato de sodio (rodenticida Guayaquil® por vía oral. Los pacientes fueron sometidos a un protocolo de manejo que incluyó canalización de vena cefálica externa a solución lactato de Ringer, así como control de las convulsio-nes con pentobarbital (10 mg/kg endovenoso como dosis inicial, después de lo cual fueron intubados. Recibieron además etanol (28%, 10 ml/kg diluidos en solución de Hartmann, gluconato de calcio (1 mg/kg en infusión y guayacolato de glicerilo (110 mg/kg, endovenoso lento. Los pacientes fueron evaluados respecto de sus constantes fisiológicas y estado neurológico según la escala Glasgow. Se mantuvo el protocolo cita-do hasta obtener ausencia de signos convulsivos, disforia y delirio. Los cinco pacientes sobrevivieron a la intoxicación y el promedio de recuperación fue de tres días. Aunque no se pudo determinar ocurrencia de secuelas neurológicas posteriores a la intoxicación, los pacientes recibieron control médico durante 15 días. El manejo oportuno del cuadro tóxico, con anticonvulsivantes, soluciones alcalinizantes, gluconato de calcio, guayacolato de glicerilo y etanol, demostraron ser efectivas como estrategias para el manejo de la intoxicación por fluoracetato de sodio.

A comparative study of preliminary dosimetry for human based on distribution data in rats with 111In, 90Y, 153Sm, and 177Lu labeled rituximab

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Radfar Edalat

2012-01-01

Full Text Available Radio immunotherapy is one of the most important and effective therapies for B-cell non Hoddgkin’s lymphoma treatment. Today, anti CD-20 antibodies labeled with beta emitter radionuclides are used in radio immunotherapy. Various radionuclides for labeling anti CD-20 antibodies have been studied and developed for the treatment and diagnosis of malignancies. This paper describes the preparation, bio-distribution and absorbed dose rate of 111In, 90Y, 177Lu, and 153Sm labeled anti CD-20 antibodies (rituximab in human organs, after injection to rats. The macro cyclic bifunctional chelating agent, N-succinimidyl-1, 4, 7, 10-tetraazacyclododecane-1, 4, 7, 10-tetraacetic acid (DOTA-NHS for conjugation to antibody, was used to prepare DOTA-rituximab. The conjugates were purified by molecular filtration, the average number of DOTA conjugated per mAb was calculated and total concentration was determined by spectrophotometric method. Radio-labeling was performed at 40 °C for 24 hours. After the quality control studies, the final radioactive solution was injected intravenously into rats through their tail vein. The tissue uptakes of each injection were measured. Then we calculated S values for 177Lu and 153Sm by using specific absorbed fractions and data used in the manner of radio-labeled analysis and dosimetry for humans. The absorbed dose rate of each organ was calculated in the specific time by medical internal radiation dose method with linear approximation in the activity measurements.

con dietas suplementadas con Cromo-L-metionina

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Ram\\u00F3n Garc\\u00EDa-Castillo

2006-01-01

Full Text Available Un total de 48 cerdos (Sus scrofa domesticus; 24 machos castrados y 24 hembras cruzados (Yorkshire, Hampshire, Duroc y Landrace de 3,5 a 4,0 meses de edad y 60,0 ± 5,0 kg PV en finalización. Se alimentaron con dietas isoproteícas (14,5 % PC e isoenergéticas (3.400 kcal EM/kg de MS, adicionadas con Cr-L-metionina (MiCroPlex® (0, 200, 400 y 600 ppb. El experimento tuvo una duración de 45 días y se realizó de agosto a noviembre del 2002 en las instalaciones de la Universidad Autónoma Agraria Antonio Narro, localizada en Saltillo, Coahuila, México. Al tener los animales aproximadamente 95 kg PV, se tomó muestra de 15 ml de sangre por cada animal para determinar la concentración de glucosa, ácido úrico, creatinina, urea, proteinas totales y colesterol. Se aplicó un diseño completamente al azar con arreglo factorial 2 x 4; dos para el factor sexo y cuatro para nivel de cromo. Los metabolitos en suero no fueron afectados (P>0,05 por el factor sexo. La glucosa en suero disminuyó (P<0,05 y el colesterol incrementó (P<0,05 con cromo en la dieta. Se concluye que el Cr incrementa el metabolismo de glucosa y disminuye el de colesterol, con lo cual puede haber energía disponible para síntesis de proteína la cual es necesaria para el crecimiento de los animales

Lepra: Sepsis en un paciente con reacción tipo II. Reporte de un caso

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Edinson Enrique Escalante Gómez

2012-08-01

Full Text Available La lepra es una patología infecciosa de carácter crónico, caracterizada por un amplio compromiso cutáneo, asociado a neuropatía, con bajas tasas de mortalidad, pero con un alto índice de discapacidad. Es causada por la infección por el bacilo, Mycobacterium leprae. A pesar que se conoce desde la antigüedad se considera un problema persistente de salud pública en áreas subtropicales donde es endémica. Su mecanismo de transmisión, es por medio de gotitas respirato-rias. Su espectro clínico es muy variado, depende de la forma en que el sistema inmunitario del huésped reacciona frente al agente infeccioso, por lo que se reconocen los polos determinados como tuberculoide y lepromatoso, una forma indeterminada y borderline. Por otro lado se considera que la reacciones lepróticas (tipo 1, tipo 2 y fenómeno de lucio son complicaciones de la hiperreactividad inmunológica que aparece cuando se afecta el equilibrio inmunológico en el huésped. En 1982 la Organización Mundial de la Salud estableció la terapia multidrogas como herramienta eficaz para el control de esta entidad. Actualmente el régimen farmacológico se establece teniendo en cuenta la clasificación que distingue al enfermo en paucibacilar y multibacilar. Presentamos un paciente masculino de 64 años, con antecedente de lepra lepromatosa multibacilar desde hace 3 años, con tratamiento irregular, suspendido 6 meses antes de clínica de ingreso consistente sepsis de origen urinario, con posterior septicemia asociada al catéter, a quien se le realiza tratamiento antibiótico de amplio espectro, con evolución satisfactoria del estado hemodinámico y manejo de la lepra ambulatorio.

Fenotipo grave en dos medio hermanas con síndrome de Adams Oliver

OpenAIRE

Sevilla-Montoya, Rosalba; Ríos-Flores, Braulio; Moreno-Verduzco, Elsa; Domínguez-Castro, Mauricio; Rivera-Pedroza, Carlos I; Aguinaga-Ríos, Dra. Mónica

2014-01-01

El síndrome de Adams Oliver (AOS) es una entidad heterogénea con defecto transverso terminal de extremidades (TTLD) y aplasia cutis congénita (ACC) con un amplio espectro fenotípico. Se han descrito diferentes modos de herencia en esta enfermedad; los defectos más graves se han asociado a un patrón autosómico recesivo (AR). Objetivo. presentar a una familia con dos medio hermanas con un fenotipo grave de Adams Oliver, con una madre sana. Reporte del caso: una mujer de 27 años de edad fue refe...

Response to rituximab-based therapy and risk factor analysis in epstein barr virus-related lymphoproliferative disorder after hematopoietic stem cell transplant in children and adults: a study from the Infectious Diseases Working Party of the European Group for Blood and Marrow Transplantation.

NARCIS (Netherlands)

Styczynski, J.; Gil, L.; Tridello, G.; Ljungman, P.; Donnelly, J.P.; Velden, W. van der; Omar, H.; Martino, R.; Halkes, C.; Faraci, M.; Theunissen, K.; Kalwak, K.; Hubacek, P.; Sica, S.; Nozzoli, C.; Fagioli, F.; Matthes, S.; Diaz, M.A.; Migliavacca, M.; Balduzzi, A.; Tomaszewska, A.; amara Rde, L. C; Biezen, A. van; Hoek, J. van den; Iacobelli, S.; Einsele, H.; Cesaro, S.

2013-01-01

BACKGROUND: The objective of this analysis was to investigate prognostic factors that influence the outcome of Epstein-Barr virus (EBV)-related posttransplant lymphoproliferative disorder (PTLD) after a rituximab-based treatment in the allogeneic hematopoietic stem cell transplant (HSCT) setting.

Cleavage of the interchain disulfide bonds in rituximab increases its affinity for FcγRIIIA.

Science.gov (United States)

Suzuki, Mami; Yamanoi, Ayaka; Machino, Yusuke; Kobayashi, Eiji; Fukuchi, Kaori; Tsukimoto, Mitsutoshi; Kojima, Shuji; Kohroki, Junya; Akimoto, Kazunori; Masuho, Yasuhiko

2013-07-05

The Fc region of human IgG1 mediates effector function via binding to Fcγ receptors and complement activation. The H and L chains of IgG1 antibodies are joined by four interchain disulfide bonds. In this study, these bonds within the therapeutic IgG1 rituximab (RTX) were cleaved either by mild reduction followed by alkylation or by mild S-sulfonation; consequently, two modified RTXs - A-RTX (alkylated) and S-RTX (S-sulfonated) - were formed, and both were almost as potent as unmodified RTX when binding CD20 antigen. Unexpectedly, each modified RTX had a higher binding affinity for FcγRIIIA (CD16A) than did unmodified RTX. However, S-RTX and A-RTX were each less potent than RTX in an assay of antibody-dependent cellular cytotoxicity (ADCC). In this ADCC assay, each modified RTX showed decreased secretion of granzyme B, but no change in perforin secretion, from effector cells. These results provide significant information on the structures within IgG1 that are involved in binding FcγRIIIA, and they may be useful in the development of therapeutic antagonists for FcγRIIIA. Copyright © 2013 Elsevier Inc. All rights reserved.

Tratamiento con implantes Leader-Nano en paciente con oligodoncia

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Salvador Javier Santos Medina

2015-03-01

Full Text Available Los implantes dentales de titanio han revolucionado el mundo de la rehabilitación desde su surgimiento. De manera particular, el empleo de implantes de carga inmediata acorta el tiempo quirúrgico y protésico, con el consiguiente bienestar estético. Se presenta el caso de una paciente femenina de 32 años de edad, con antecedentes de oligodoncia de ambos incisivos laterales superiores y portadora de prótesis parcial acrílica. Fue atendida por el equipo multidisciplinario de implantes en la Clínica Estomatológica Docente “3 de Octubre” y se le realizó tratamiento de rehabilitación integral con implantes Leader-Nano y prótesis fija con corona acrílica sobre dichos implantes. La implantología fue satisfactoria en la paciente; la mejoría estética y funcional, así como la satisfacción de la paciente, fueron los principales logros obtenidos

pacientes con insuficiencia renal terminal

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Karen Herrera Herrera

2011-01-01

Full Text Available La presente investigación fundamenta en la clínica psicoanalítica el estudio de dos casos de tres personas diagnosticadas con IRT que reciben tratamiento de hemodiálisis, en razón a que dadas las características y el aumento de los reportes que se presentan, ya esto se considera un problema de salud pública. El objetivo principal es describir las características dinámicas del proceso de duelo en pacientes con IRT en un centro de terapia renal de la ciudad de Cartagena. El procedimiento metodológico empleó un diseño de tipo cualitativo; la investigación se desarrolló con un diseño clínico mediante el estudio de casos, y fundamentada en la hermenéutica psicoanalítica. Todo esto respaldado en la historia clínica, la entrevista semiestructurada individual y familiar, los test proyectivos, test del dibujo de la figura humana Machover y TAT de Murray, para la debida integración de los análisis. Se concluye que predominan funciones fallidas de los progenitores y que son individuos provenientes de familias psicosomáticas, que utilizan la enfermedad para obtener un beneficio secundario.

Experiencias de haber crecido con un padre/madre con trastorno mental severo (TMS)

OpenAIRE

Vivanco B, Gabriela; Grandón F, Pamela

2016-01-01

Introducción. La experiencia de vivir con personas que presentan un Trastorno Mental Severo (TMS) es difícil para las familias, en especial para los hijos quienes han sido poco estudiados. El objetivo de la investigación fue conocer cómo la experiencia de haber vivido con un padre o madre con un trastorno mental severo influyó en la infancia, adolescencia y adultez joven de sus hijos e hijas. Método. Se analizan las experiencias de convivencia con un padre/madre con TMS en 10 hijos (6 hombres...

Long-term efficacy and safety of rituximab in IgG4-related disease: Data from a French nationwide study of thirty-three patients.

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Mikael Ebbo

Full Text Available To assess efficacy and safety of rituximab (RTX as induction therapy, maintenance of remission and treatment of relapses in a cohort of IgG4-related disease (IgG4-RD patients.Nationwide retrospective multicenter study of IgG4-RD patients treated with at least one course of RTX. Clinical, biological and radiological response, relapse rate and drug tolerance were analyzed. Kaplan-Meier curves were plotted and risk factors for relapse studied with a Cox regression model.Among 156 IgG4-RD patients included in the French database, 33 received rituximab. Clinical response was noted in 29/31 (93.5% symptomatic patients. Glucocorticoids withdrawal was achieved in 17 (51.5% patients. During a mean follow-up of 24.8 ±21 months, 13/31 (41.9% responder patients relapsed after a mean delay of 19 ±11 months after RTX. Active disease, as defined by an IgG4-RD Responder Index >9 before RTX, was significantly associated with relapse (HR = 3.68, 95% CI: 1.1, 12.6 (P = 0.04, whereas maintenance therapy with systematic (i.e. before occurrence of a relapse RTX retreatment was associated with longer relapse-free survival (41 versus 21 months; P = 0.02. Eight severe infections occurred in 4 patients during follow-up (severe infections rate of 12.1/100 patient-years and hypogammaglobulinemia ≤5 g/l in 3 patients.RTX is effective for both induction therapy and treatment of relapses in IgG4-RD, but relapses are frequent after B-cell reconstitution. Maintenance therapy with systematic RTX infusions is associated with longer relapse-free survival and might represent a novel treatment strategy. Yet, the high rate of infections and the temporary effect of RTX might be hindrances to such strategy.

Long-term efficacy and safety of rituximab in IgG4-related disease: Data from a French nationwide study of thirty-three patients

Science.gov (United States)

Grados, Aurélie; Samson, Maxime; Groh, Matthieu; Loundou, Anderson; Rigolet, Aude; Terrier, Benjamin; Guillaud, Constance; Carra-Dallière, Clarisse; Renou, Frédéric; Pozdzik, Agnieszka; Labauge, Pierre; Palat, Sylvain; Berthelot, Jean-Marie; Pennaforte, Jean-Loup; Wynckel, Alain; Lebas, Céline; Le Gouellec, Noémie; Quémeneur, Thomas; Dahan, Karine; Carbonnel, Franck; Leroux, Gaëlle; Perlat, Antoinette; Mathian, Alexis; Cacoub, Patrice; Hachulla, Eric; Costedoat-Chalumeau, Nathalie; Harlé, Jean-Robert; Schleinitz, Nicolas

2017-01-01

Objectives To assess efficacy and safety of rituximab (RTX) as induction therapy, maintenance of remission and treatment of relapses in a cohort of IgG4-related disease (IgG4-RD) patients. Methods Nationwide retrospective multicenter study of IgG4-RD patients treated with at least one course of RTX. Clinical, biological and radiological response, relapse rate and drug tolerance were analyzed. Kaplan-Meier curves were plotted and risk factors for relapse studied with a Cox regression model. Results Among 156 IgG4-RD patients included in the French database, 33 received rituximab. Clinical response was noted in 29/31 (93.5%) symptomatic patients. Glucocorticoids withdrawal was achieved in 17 (51.5%) patients. During a mean follow-up of 24.8 ±21 months, 13/31 (41.9%) responder patients relapsed after a mean delay of 19 ±11 months after RTX. Active disease, as defined by an IgG4-RD Responder Index >9 before RTX, was significantly associated with relapse (HR = 3.68, 95% CI: 1.1, 12.6) (P = 0.04), whereas maintenance therapy with systematic (i.e. before occurrence of a relapse) RTX retreatment was associated with longer relapse-free survival (41 versus 21 months; P = 0.02). Eight severe infections occurred in 4 patients during follow-up (severe infections rate of 12.1/100 patient-years) and hypogammaglobulinemia ≤5 g/l in 3 patients. Conclusion RTX is effective for both induction therapy and treatment of relapses in IgG4-RD, but relapses are frequent after B-cell reconstitution. Maintenance therapy with systematic RTX infusions is associated with longer relapse-free survival and might represent a novel treatment strategy. Yet, the high rate of infections and the temporary effect of RTX might be hindrances to such strategy. PMID:28915275

Epilepsia de la infancia con paroxismos occipitales

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Albia Pozo Alonso

1999-09-01

Full Text Available Se reporta que la epilepsia de la infancia con paroxismos occipitales constituye un síndrome epiléptico muy bien definido; se incluye en el grupo de las epilepsias idiopáticas relacionadas con localización. Los ataques comienzan habitualmente con síntomas visuales, en ocasiones seguidos por ataques hemiclónicos, parciales complejos y tónicoclónicos generalizados. El electroencefalograma interictal muestra complejos de puntaonda de localización occipital y temporal posterior que desaparecen con la apertura de los ojos. Se presenta una paciente de 8 años de edad que reúne los criterios clínicos y electroencefalográficos de la epilepsia de la infancia con paroxismos occipitales y se enfatiza en la evolución supuestamente benigna de dicho síndrome.Is is reported that epilepsy of childhood with occipital paroxysms is an epileptic syndrome that is well defined. It is included in the group of related idiopathic epilepsies with localization. Seizures habitually begin with visual symptoms, which are ocassionally followed by hemiclonic, complex partial, and generalized tonicclonic seizures. The interictal EEG shows spike-wave complexes of occipital and temporal posterior localization that are suppressed by eye opening. A patient aged 8 in whom the clinical and electroencephalographic criteria of epilepsy of childhood with occipital paroxysms are present is studied in this paper. Emphasis is made on the apparently benign evolution of this syndrome.

Acanthamoeba sp.: un caso de queratitis no relacionada con el uso de lentes de contacto Acanthamoeba sp.: a case report in a non-contact lens wearer

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Claudia Menghi

2012-12-01

Full Text Available La queratitis por Acanthamoeba sp. generalmente se relaciona con el uso de lentes de contacto y en menor proporción se vincula con el contacto con agua contaminada. Se caracteriza por una disminución de la capacidad visual y la presencia de un fuerte dolor ocular. al examen clínico, puede confundirse con una infección herpética. Si la infección no es diagnosticada y tratada a tiempo en forma adecuada, puede culminar en la perforación de la córnea y, eventualmente, en la pérdida del ojo. en este trabajo se informa uno de los pocos casos registrados de queratitis por Acanthamoeba sp. no relacionada con el uso de lentes de contacto.Acanthamoeba sp. keratitis is generally related to wearing contact lenses, and, to a lesser extent, to contaminated water. it is characterized by reduced visual capacity and the presence of severe ocular pain. Clinically, it can be mistaken for a herpes infection. if it is not diagnosed, and timely and adequately treated, it can result in corneal perforation and, eventually, in vision loss. One of the few registered cases of Acanthamoeba sp. keratitis not related to the use of contact lenses is herein reported.

Fish stakes: the pros and cons of the Marine Stewardship Council initiative: a debate from the pages of SAMUDRA Report

OpenAIRE

1998-01-01

The recent effort by two global organizations, the World Wide Fund for Nature (WWF) and the Anglo-Dutch multinational, Unilever, to establish an independent Marine Stewardship Council (MSC) as a conservation partnership to create market incentives for sustainable fishing has attracted a great deal of attention-as well as controversy. In this dossier, the pros and cons of the SC initiative are argued out in a series of articles that first appeared in SAMUDRA Report, the triannual publication o...

Expression of CD40 is a positive prognostic factor of diffuse large B-cell lymphoma treated with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone

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Song G

2016-06-01

Full Text Available Guoqi Song,1 Huiyun Ni,1 Linqing Zou,2 Shukui Wang,3 Fuliang Tian,4 Hong Liu,1 William C Cho5 1Department of Hematology, Affiliated Hospital of Nantong University, Nantong, 2Department of Human Anatomy, Nantong University, Nantong, 3Central Laboratory of Nanjing First Hospital, Nanjing Medical University, Nanjing, 4Maternal and Child Health Hospital of Lianyungang, Lianyungang, Jiangsu, People’s Republic of China; 5Department of Clinical Oncology, Queen Elizabeth Hospital, Kowloon, Hong Kong Objectives: The objective of this study was to investigate the expression level of CD40 and its role in the prognosis of patients with diffuse large B-cell lymphoma (DLBCL who were treated with rituximab-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone.Design and methods: The immunohistochemical expressions of CD40 in 186 well-characterized DLBCL patients were evaluated by tissue microarrays, thereby revealing the relationship of the molecule CD40 with known tumor, patient-related variables, and survival rates.Results: The results showed that CD40 expressions were not statistically different between the germinal center B-cell-like (GCB type and the non-GCB type. We also analyzed the relationships of CD40 expression with overall survival (OS and progression-free survival (PFS in DLBCL patients who were uniformly treated with R-CHOP. A low expression of CD40 compared to high expression is related to poor OS and PFS. Conclusion: Our findings indicate that the CD40 level at onset acts as an independent prognostic predictor of DLBCL patients treated with R-CHOP. Keywords: CD40, diffuse large B-cell lymphoma, R-CHOP, prognostic factor

Hiperoxaluria primaria con pancitopenia: a propósito de un caso

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Jessica Bravo Zuñiga

2005-06-01

Full Text Available Se presenta el caso de un varón, de 15 años de edad, con diagnóstico de litiasis renal desde la infancia que evolucionó a Insuficiencia Renal Crónica, requiriendo hemodiálisis. Seis meses antes del reporte se agregan dolores articulares, con signos flogósicos en rodilla derecha, compromiso progresivo del estado general, pérdida de peso y anemia. Al examen físico se encuentra a un paciente emaciado, pálido, con múltiples adenopatías cervicales, y presencia de hepato-esplenomegalia. Se realizan exámenes evidenciándose: pancitopenia, con mayor compromiso de la serie roja (hemoglobina 7,3mg/dL, leucocitos 2 600/µL, y plaquetas 123 000/µL.. Los valores de transaminasas y bilirrubinas fueron normales así como los dosajes de Fierro, Transferrina, Ácido Fólico y Vitamina B12. La ecografía abdominal revela riñones calcificados y atróficos y los Rx de abdómen demuestran nefrocalcinosis y litiasis renal. La biopsia de medula ósea evidenció un extenso depósito de cristales de oxalato de calcio, dispuestos en forma radiada, con casi completa obliteración de la medula ósea con un número variable de células multinucleadas y fibrosis moderada. El aspirado de medula ósea no mostró cristales de oxalato de calcio. Este reporte hace una revisión sobre hiperoxaluria primaria, y resalta la importancia de reconocer la enfermedad como causa de falla renal en un paciente con historia clínica de litiasis renal y nefrocalcinosis. (Rev Med Hered 2004;16:148-156

Rationale and design of the RIACT–study: a multi-center placebo controlled double blind study to test the efficacy of RItuximab in Acute Cellular tubulointerstitial rejection with B-cell infiltrates in renal Transplant patients: study protocol for a randomized controlled trial

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Schiffer Lena

2012-10-01

Full Text Available Abstract Background Acute kidney allograft rejection is a major cause for declining graft function and has a negative impact on the long-term graft survival. The majority (90% of acute rejections are T-cell mediated and, therefore, the anti-rejection therapy targets T-cell-mediated mechanisms of the rejection process. However, there is increasing evidence that intragraft B-cells are also important in the T-cell-mediated rejections. First, a significant proportion of patients with acute T-cell-mediated rejection have B-cells present in the infiltrates. Second, the outcome of these patients is inferior, which has been related to an inferior response to the conventional anti-rejection therapy. Third, treatment of these patients with an anti-CD20 antibody (rituximab improves the allograft outcome as reported in single case observations and in one small study. Despite the promise of these observations, solid evidence is required before incorporating this treatment option into a general treatment recommendation. Methods/Design The RIACT study is designed as a randomized, double-blind, placebo-controlled, parallel group multicenter Phase III study. The study examines whether rituximab, in addition to the standard treatment with steroid-boli, leads to an improved one-year kidney allograft function, compared to the standard treatment alone in patients with acute T-cell mediated tubulointerstitial rejection and significant B-cell infiltrates in their biopsies. A total of 180 patients will be recruited. Discussion It is important to clarify the relevance of anti-B cell targeting in T-cell mediated rejection and answer the question whether this novel concept should be incorporated in the conventional anti-rejection therapy. Trial registration Clinical trials gov. number: NCT01117662

Challenges in economic evaluation of new drugs: experience with rituximab in Hungary.

Science.gov (United States)

Brodszky, Valentin; Orlewska, Ewa; Pentek, Martha; Karpati, Krisztian; Skoupa, Jana; Gulacsi, Laszlo

2010-01-01

Implementation of a new therapy into clinical practice is a complex process. Various countries have different requirements for information but most often focus on economic evaluation, which often plays a stronger role in healthcare decision making than does clinical evidence. To identify all potential challenges in economic evaluation, the case of a new biological drug, rituximab, used to treat rheumatoid arthritis, has been taken as an example. We present methods and results of economic assessment, highlighting the specific issues that should be considered in countries with economic and health care conditions similar to those of Hungary. In principle, economic evaluation requires data on characteristics of target population, disease progression, treatment impact, preferences, resource utilization and unit prices. Treatment effect/relative risk reduction and clinical practice patterns (resource use) may be more generalizable, whereas prices and baseline risk need to be jurisdiction specific. In order to address issues of transferability, investments need to be made in the collection of epidemiological and demographic data, plus data on clinical practice patterns, resource use, costs and health state valuation. In Hungary this problem has been solved through conducting a well designed 255 patient cross-sectional study. The Hungarian example shows that there should be more investment in data collection for those parameters that are thought to differ most from place to place. Owing to the similarities between Central and Eastern Europe countries in health care systems, clinical practice patterns and economic indicators, they may be able to develop partnerships to develop relevant regional databases and registries.

Aspectos Psicosociales Relacionados con el TEPT en Pacientes con Cáncer de Mama

OpenAIRE

Hernández Moreno, Fresia Paloma; Landero Hernández, René

2015-01-01

El objetivo del estudio fue analizar la relación del estrés, la depresión y las estrategias de afrontamiento con el Trastorno de Estrés Postraumático (TEPT) en una muestra de pacientes con cáncer de mama. Se realizó con una muestra no probabilística de 52 mujeres con cáncer de mama. Se encontró una relación entre TEPT y estrés (r= .344, p= .014), TEPT y depresión (rs=.346, p= .013). El TEPT correlacionó con evitación cognitiva (r= .437, p= .001), TEPT y desesperanza (rs= .437, p= .001) y TEPT...

Recovery from severe dysphagia in systemic sclerosis - myositis overlap: a case report.

Science.gov (United States)

Chinniah, Keith J; Mody, Girish M

2017-06-01

Dysphagia is common in inflammatory myopathies and usually responds to corticosteroids. Severe dysphagia requiring feeding by percutaneous endoscopic gastrostomy is associated with significant morbidity and high mortality. A 56-year old African Black woman initially presented with systemic sclerosis (SSC) - myositis overlap and interstitial lung disease. She responded to high dose corticosteroids and cyclophosphamide followed by azathioprine, with improvement in her lung function and regression of the skin changes. Six years later she had a myositis flare with severe dysphagia. Her myositis improved after high doses of corticosteroids, azathioprine and two doses of intravenous immunoglobulin (IVIG). As her dysphagia persisted, she was fed via a percutaneous endoscopic gastrostomy (PEG) tube and given a course of rituximab. Her dysphagia gradually resolved and the PEG tube was removed within two months. She received another dose of rituximab six months later and continued low dose prednisone and azathioprine. Her muscle power improved, weight returned to normal and she remained well 20 months after hospital discharge. Our patient with SSC-myositis overlap and severe dysphagia requiring PEG feeding, improved with high dose corticosteroids, azathioprine, two courses of IVIG and rituximab, and remained in remission 20 months after hospital discharge.

Microthrombotic renal involvement in an SLE patient with concomitant catastrophic antiphospholipid syndrome: the beneficial effect of rituximab treatment.

Science.gov (United States)

Diószegi, Á; Tarr, T; Nagy-Vincze, M; Nánásy-Vass, M; Veisz, R; Bidiga, L; Dezső, B; Balla, J; Szodoray, P; Szekanecz, Z; Soltész, P

2018-01-01

Antiphospholipid syndrome is characterized by multiple arterial and/or venous thrombotic events, recurrent fetal losses in the presence of antiphospholipid antibodies (aPL). Catastrophic antiphospholipid syndrome is a life-threatening, rare subset of antiphospholipid syndrome when the thrombotic events affect at least three organs, and clinical manifestations develop simultaneously or within a week. Diagnostically, small vessel occlusions can be detected by histopathology in the presence of aPL. Our case report describes an 18-year-old man who has been treated for antiphospholipid syndrome associated with systemic lupus erythematosus (SLE) since 2011. The clinical findings were dominated by recurrent deep vein thrombosis, and severe proteinuria caused by lupus nephritis, accompanied by mild serological and laboratory findings. The patient was hospitalized in March 2014 because of severe thrombocytopenia and infective diarrhoea. At this time the renal functions deteriorated rapidly. Simultaneously, left upper extremity paresis was observed; computed tomography showed ischaemic lesions in the territory of the middle cerebral artery. Abdominal discomfort and pain occurred. On computed tomography scan ischaemic lesions were seen in the spleen, the right kidney and the coeliac trunk. Laboratory and serological findings verified the presence of aPL and anti-DNA antibodies, anaemia and thrombocytopenia. Based on the above-mentioned clinical and laboratory findings, the diagnosis of catastrophic antiphospholipid syndrome was established. Anticoagulation, corticosteroids and plasma exchange treatment, as well as haemodiafiltration were initiated. Although the thrombotic cascade decelerated following these interventions, we could not see an improvement in the renal function. Rituximab treatment was started, leading to a significant improvement in renal function. After 5 weeks of treatment the patient was discharged from hospital.

Dislipidemia en pacientes con artritis reumatoide atendidos en un hospital general

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Jose Galindo

2011-04-01

Full Text Available Objetivo: Determinar la frecuencia de dislipidemia en pacientes con artritis reumatoide (AR atendidos en un hospital general. Material y métodos: Estudio observacional, descriptivo y transversal. Se incluyeron 44 pacientes a quienes se les determinó perfil lipídico sérico. Los resultados se clasificaron según el reporte modificado en el 2004 del tercer panel de tratamiento del adulto (ATP III. Además, se determinó el índice de masa corporal (IMC, la puntuación para la actividad de la enfermedad (DAS-28 y la limitación funcional medida con el cuestionario de evaluación de salud - versión peruana (HAQ-P. Resultados: La frecuencia de dislipidemia en pacientes con AR fue 75%. El 54,5% tuvo un IMC fuera de los límites normales. En el DAS-28, la mayoría de pacientes se encontraron con actividad severa de la enfermedad. Sin embargo, hubo más pacientes con dislipidemia en el grupo con moderada actividad. En la escala de HAQ-P, la mitad tuvo incapacidad funcional moderada a severa y mayor número de sujetos con dislipidemia. El 69,7% de los pacientes con alteraciones en el perfil lipídico presentó dislipidemia mixta. Conclusiones: La dislipidemia en los pacientes con AR del estudio se presentó con una alta frecuencia y con diversas formas de alteración en el perfil lipídico sin un patrón uniforme. Por lo tanto, el tratamiento de la dislipidemia sería individualizado en cada paciente para prevenir eventos cardiovasculares.(Rev Med Hered 2011;22:47-53.

Rehabilitación de paciente fumador con prótesis hibrida sobre seis implantes: Reporte de caso

OpenAIRE

López López, Carmen Eliana; Quintana del Solar, Martin

2016-01-01

La prótesis sobre implantes es una buena alternativa de tratamiento frente a los tratamientos convencionales de prótesis total en pacientes con edentulismo total. Este tratamiento se ha venido realizando con éxito en losúltimos años y constituye una realidad clínica de alto valor. El presente artículo reporta el caso clínico de un paciente de sexo masculino fumador donde se realizó la rehabilitación del maxilar superior con una prótesis tipohibrida sobre 6 implantes. A continuación se describ...

Embarazo abdominal avanzado con feto vivo: Reporte de un caso y revisión de la literatura

OpenAIRE

Gélvez-Téllez, Samuel

2015-01-01

Objetivos: describir el caso de una paciente con embarazo abdominal a término y feto vivo, y realizar una revisión de la literatura sobre el diagnóstico y tratamiento, con énfasis en la extracción de la placenta y el uso de metotrexate para el manejo de la placenta residual. Materiales y métodos: se presenta el caso de una paciente con un embarazo abdominal avanzado de 38 semanas y 5 días de gestación, atendida en un hospital público de referencia de mediana complejidad, ubicado en el departa...

Paciente con esquizofrenia tratado con ziprasidona + clozapina

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Pol Yanguas E.

2013-05-01

Full Text Available P es un paciente diagnosticado de esquizofrenia, sigue en un piso tutelado un programa de rehabilitación, está medicado con clozapina 500 mg/día y ziprasidona 280 mg/ día. Padece hipercolesterolemia, tabaquismo y sus hábitos alimenticios no son buenos. La medicación que utiliza desde 2007 hasta ahora se refleja en la tabla 1. El último tratamiento se le introdujo el 7 de agosto de 2012, habiendo presentado un electro cardiograma (ECG normal, pero con ligera taquicardia ventricular y prolactinemia de 44,8 ng/ml (valores normales: 2-18 ng/ml.

Characterization of CD4 T Cell Epitopes of Infliximab and Rituximab Identified from Healthy Donors

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Moustafa Hamze

2017-05-01

Full Text Available The chimeric antibodies anti-CD20 rituximab (Rtx and anti-TNFα infliximab (Ifx induce antidrug antibodies (ADAs in many patients with inflammatory diseases. Because of the key role of CD4 T lymphocytes in the initiation of antibody responses, we localized the CD4 T cell epitopes of Rtx and Ifx. With the perspective to anticipate immunogenicity of therapeutic antibodies, identification of the CD4 T cell epitopes was performed using cells collected in healthy donors. Nine T cell epitopes were identified in the variable chains of both antibodies by deriving CD4 T cell lines raised against either Rtx or Ifx. The T cell epitopes often exhibited a good affinity for human leukocyte antigen (HLA-DR molecules and were part of the peptides identified by MHC-associated peptide proteomics assay from HLA-DR molecules of dendritic cells (DCs loaded with the antibodies. Two-third of the T cell epitopes identified from the healthy donors stimulated peripheral blood mononuclear cells from patients having developed ADAs against Rtx or Ifx and promoted the secretion of a diversity of cytokines. These data emphasize the predictive value of evaluating the T cell repertoire of healthy donors and the composition of peptides bound to HLA-DR of DCs to anticipate and prevent immunogenicity of therapeutic antibodies.

Riesgo familiar total en familias con mujeres diagnosticadas con neoplasia de mama

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Nancy Cecilia Charrys-Bravo

2017-07-01

Full Text Available Objetivo: Determinar el riesgo familiar total de las familias con mujeres diagnosticadas con cáncer de mama, que asisten a un centro de salud oncológico en la ciudad de Barranquilla. Materiales y Métodos: El estudio fue de tipo descriptivo, transversal con abordaje cuantitativo. Se utilizó el instrumento Riesgo Familiar Total RFT 5-33. El universo estuvo conformado por familias con mujeres diagnosticadas con cáncer en mama. La muestra fue de 41 familias que integraron a 154 miembros; se abordó el estudio de manera censal, y no por medio de una muestra, porque el acceso a la información de la totalidad de las familia fue viable. Resultados: Los resultados mostraron que las familias, en su mayoría, son de tipo 2. El 68 % de las pacientes categorizan sus familias como amenazadas, el 5 % como familias de alto riesgo y un 27 % de las familias con un bajo riesgo. Conclusiones: Los hallazgos encontrados en esta investigación son importantes para las familias, lo cual permitirá establecer acciones y actividades que logren orientar e implementar procesos de atención específicos con el propósito de cuidar a las familias para que se mantengan sanos en un nivel de bajo riesgo; además, desarrollar controles y seguimiento a aquellas familias que se encuentran en un riesgo alto de amenazas, mediante acciones de promoción y prevención de la enfermedad de una manera amplia. Por lo anterior, se deben emprender programas más agresivos de prevención y promoción, especialmente con las familias que asisten en busca de apoyo médico para este padecimiento; de esta forma, se podrán diagnosticar los casos de forma temprana y proceder al respectivo tratamiento.

Intoxicación con cocaína: reporte de caso

OpenAIRE

Juan Dávila Meneses

2013-01-01

El consumo de cocaína en Costa Rica, en cualquiera de sus presentaciones, es un problema creciente de salud pública y seguridad ciudadana desde la década de los 80’s. Las complicaciones derivadas de su uso tienen un impacto considerable en la utilización del recurso humano y económico de nuestro sistema de salud y cuya complejidad de manejo es clara: se ha asociado en forma muy importante con la muerte súbita en pacientes jóvenes y sin factores de riesgo, que presentan infartos agudos del mio...

REDUCCIÓN DE ÓXIDOSDE NITROGENO CON CATALIZADORES ZEOLÍTICOS INTERCAMBIADOS CON COBALTO

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Enrique Alexis García Moya

2012-10-01

Full Text Available Se presenta un estudio sobre la reducción catalítica selectiva (RCS de NOx con metano en presencia de oxígeno en exceso con varios catalizadores a base de las zeolitas mordenita, ferrierita y ZSM-5 intercambiadas con diferentes cargas de cobalto y con las correspondientes zeolitas en forma acida. Cuando la mezcla reactiva contenía mayormente NO2 en lugar de NO, los catalizadores ácidos mostraron las más altas velocidades de formación de N2 en condiciones secas. Las mayores actividades se obtuvieron con los catalizadores Co-mordenita, siguiendo en orden de actividad los catalizadores Co-Ferrierita y Co-ZSM-5. El catalizador Co-Mordenita más activo se ensayó con una mezcla reactiva donde predominó el NO en lugar del NO2 bajo condiciones secas e hidrotérmicas y en presencia de SO2. Con la adición de 8% de agua a la mezcla de reacción se observó desactivación reversible, especialmente a bajas temperaturas. La adición de 60 ppm de SO2 disminuyó la velocidad de reacción aproximadamente a la mitad debido posiblemente al envenenamiento de algunos sitios activos.

Expression of Tissue factor in Adenocarcinoma and Squamous Cell Carcinoma of the Uterine Cervix: Implications for immunotherapy with hI-con1, a factor VII-IgGFc chimeric protein targeting tissue factor

International Nuclear Information System (INIS)

Cocco, Emiliano; Azodi, Masoud; Schwartz, Peter E; Rutherford, Thomas J; Pecorelli, Sergio; Lockwood, Charles J; Santin, Alessandro D; Varughese, Joyce; Buza, Natalia; Bellone, Stefania; Glasgow, Michelle; Bellone, Marta; Todeschini, Paola; Carrara, Luisa; Silasi, Dan-Arin

2011-01-01

Cervical cancer continues to be an important worldwide health problem for women. Up to 35% of patients who are diagnosed with and appropriately treated for cervical cancer will recur and treatment results are poor for recurrent disease. Given these sobering statistics, development of novel therapies for cervical cancer remains a high priority. We evaluated the expression of Tissue Factor (TF) in cervical cancer and the potential of hI-con1, an antibody-like-molecule targeted against TF, as a novel form of immunotherapy against multiple primary cervical carcinoma cell lines with squamous- and adenocarcinoma histology. Because TF is a transmembrane receptor for coagulation factor VII/VIIa (fVII), in this study we evaluated the in vitro expression of TF in cervical carcinoma cell lines by immunohistochemistry (IHC), real time-PCR (qRT-PCR) and flow cytometry. Sensitivity to hI-con1-dependent cell-mediated-cytotoxicity (IDCC) was evaluated in 5-hrs- 51 chromium-release-assays against cervical cancer cell lines in vitro. Cytoplasmic and/or membrane TF expression was observed in 8 out of 8 (100%) of the tumor tissues tested by IHC and in 100% (11 out of 11) of the cervical carcinoma cell lines tested by real-time-PCR and flow cytometry but not in normal cervical keratinocytes (p = 0.0023 qRT-PCR; p = 0.0042 flow cytometry). All primary cervical cancer cell lines tested overexpressing TF, regardless of their histology, were highly sensitive to IDCC (mean killing ± SD, 56.2% ± 15.9%, range, 32.4%-76.9%, p < 0.001), while negligible cytotoxicity was seen in the absence of hI-con1 or in the presence of rituximab-control-antibody. Low doses of interleukin-2 further increased the cytotoxic effect induced by hI-con1 (p = 0.025) while human serum did not significantly decrease IDCC against cervical cancer cell lines (p = 0.597). TF is highly expressed in squamous and adenocarcinoma of the uterine cervix. hI-con1 induces strong cytotoxicity against primary cervical cancer cell

Terapias alternativas con animales para niños con necesidades especiales

OpenAIRE

Cea-Chueca, Aihnoa

2014-01-01

El presente trabajo de fin de grado consiste en la realización de un análisis y descripción de la literatura acerca de las distintas terapias animales, destinadas a niños con necesidades especiales: cómo y por qué surgieron, en qué consisten las terapias, cómo podemos utilizarlas, etc. Las terapias alternativas con animales se conocen como una alternativa terapéutica, donde se utiliza a un animal como co-terapeuta para poder desarrollar diferentes capacidades de los niños con necesidades espe...

Manejo exitoso de hernia diafragmática congénita con ECMO. Primer reporte de caso en México

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Ulises Garza-Serna

2017-11-01

Full Text Available INTRODUCCIÓN: la hernia diafragmática congénita es una enfermedad que afecta a 1 de 3000 recién nacidos, con un alto índice de morbilidad y mortalidad, especialmente si se presenta con otras malformaciones como las anomalías congénitas cardiacas. El manejo del paciente con este padecimiento debe ser tratado de forma multidisciplinaria e incluir su evaluación prenatal y atención posnatal. OBJETIVO: reportar el primer caso exitoso en México de un paciente con hernia diafragmática congénita manejado con membrana de oxigenación extracorpórea. CASO CLÍNICO: paciente masculino de 37.5 semanas de gestación con diagnóstico prenatal de hernia diafragmática congénita a las 24 semanas de gestación sin otras anomalías congénitas; índice pulmón/ cabeza de 1.7. A las seis horas de nacido presentó saturación de oxígeno preductal de 78% y posductal a 58% con índice de oxigenación de 41, a pesar del tratamiento agresivo médico y ventilatorio, por lo que se necesitó la intervención e implementación de la membrana de circulación extracorpórea.

In Vitro Methods for Comparing Target Binding and CDC Induction Between Therapeutic Antibodies: Applications in Biosimilarity Analysis.

Science.gov (United States)

Salinas-Jazmín, Nohemi; González-González, Edith; Vásquez-Bochm, Luz X; Pérez-Tapia, Sonia M; Velasco-Velázquez, Marco A

2017-05-04

Therapeutic monoclonal antibodies (mAbs) are relevant to the treatment of different pathologies, including cancers. The development of biosimilar mAbs by pharmaceutical companies is a market opportunity, but it is also a strategy to increase drug accessibility and reduce therapy-associated costs. The protocols detailed here describe the evaluation of target binding and CDC induction by rituximab in Daudi cells. These two functions require different structural regions of the antibody and are relevant to the clinical effect induced by rituximab. The protocols allow the side-to-side comparison of a reference rituximab and a marketed rituximab biosimilar. The evaluated products showed differences both in target binding and CDC induction, suggesting that there are underlying physicochemical differences and highlighting the need to analyze the impact of those differences in the clinical setting. The methods reported here constitute simple and inexpensive in vitro models for the evaluation of the activity of rituximab biosimilars. Thus, they can be useful during biosimilar development, as well as for quality control in biosimilar production. Furthermore, the presented methods can be extrapolated to other therapeutic mAbs.

Tratamiento Temprano de la Maloclusión Clase III con aparatología Ortopédica: Reporte de caso con 7 años de control

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Alzate-J

2014-01-01

Full Text Available Una de las maloclusiones más complejas de diagnosticar y de tratar es la maloclusión clase III.\tSe caracteriza por una alteración en la relación sagital de los maxilares, ya sea por una deficiencia o retrusión maxilar o por un prognatismo o macrognatismo mandibular, o bien sea una combinación de las anteriores. La etiología es multifactorial y es debida a una interacción de factores hereditarios y ambientales. Se presenta una paciente de 4 años de edad, sexo femenino, con patrón hereditario de clase III en su familia materna. Relación esquelética clase III con mandíbula aumentada en longitud, protruida, rotando posterior y maxilar superior retruído. Tipo de crecimiento vertical, con un perfil recto y mordida cruzada anterior y posterior unilateral izquierda. Se instauró tratamiento con aparatología ortopédica durante el periodo de dentición decidua hasta la dentición permanente, para lograr así, equilibrar el crecimiento maxilomandibular. Uno de los aspectos clínicos más complicados del manejo ortopédico de la maloclusión clase III es la recidiva después del período de tratamiento activo; sin embargo en nuestra paciente se consiguen cambios a nivel esquelético, dental y estéticos que se mantuvieron durante el tratamiento

Beneficios del cinc en el tratamiento de niños con diarrea

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Francisco José Sabatier García

1997-12-01

Full Text Available Se realizó un estudio prospectivo en 110 pacientes con enfermedad diarreica, los cuales recibieron suplementación con sulfato de cinc, a la dosis de 2 mg/kg/día, con el propósito de evaluar cómo influye en la evolución de la enfermedad. Se pudo comprobar que con la administración de este micronutriente se disminuye la duración del episodio diarreico y la estadía hospitalaria, además de que se reduce el número de deposiciones. Se discuten los resultados tomando como referencia los reportes de la literatura médica. No hubo efectos adversos con el uso de este oligoelemento.A prospective study on 110 patients presenting with diarrhea was conducted. Patients received supplements with zinc sulfate in a dose of 2 mg/kg/day with the aim of evaluate the influence of this compound in the course of the disease. It was demonstrated that with the administration of this nutrient it is possible to reduce the duration of the diarrheal episode as well as hospital stay. In addition, the number of stools is also reduced. Results are discussed taking the reports available in the medical literature as references. There were no adverse effects with the use of this trace element.

Adolescente con inestabilidad lumbosacra por presencia de quiste hidatídico: reporte de caso

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Miguel Vizcarra

Full Text Available La hidatidosis, causada por el Echinococcus granulosus, afecta a la columna vertebral en 0,5-2% del total de casos, siendo la columna sacra una ubicación rara, típica de personas en edad adulta. Se reporta el caso de un varón de 14 años oriundo de Juliaca (Puno, Perú quien presentó lumbalgia crónica y síndrome de cauda equina. Atendido inicialmente en Juliaca, fue trasladado al Hospital Edgardo Rebagliati Martins (Lima, Perú con el diagnóstico de tumoración sacra. En la resonancia magnética se mostró una tumoración multiquística con lisis del L5 y S1 e inestabilidad. El tratamiento quirúrgico fue una laminectomía L5-S2 y extracción de múltiples quistes de hidátide más estabilización lumbopélvica con tornillos transpediculares. En el posoperatorio se recetó albendazol (15 mg/kg/d por el periodo de seis meses. Se debe considerar al quiste hidatídico dentro del diagnóstico diferencial cuando existan lesiones quísticas en la columna vertebral, sobre todo en regiones endémicas como el Perú.

Variables socionutricionales de hogares mazahuas integrados por preescolares desnutridos con madres con obesidad y sin obesidad

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Conzuelo González, Viridiana Vanessa

2009-01-01

Full Text Available El primer objetivo fue conocer cuántos menores de cinco años con diferentes grados de desnutrición tienen una madre con sobrepeso/obesidad/ en una comunidad indígena que vive en extrema pobreza y bajo condiciones de migración masculina internacional. El segundo fue comparar tres variables socionutricionales (ingreso familiar, educación de la madre y adecuación nutrimental de la dieta diaria entre estos hogares y los hogares con desnutrición infantil y madres sin obesidad. Se realizó un estudio transversal (2006-2007, en la comunidad mazahua de San Francisco Tepeolulco, Municipio de Temascalcingo; que incluyó a 85 hogares integrados por preescolares con desnutrición inscritos al programa Oportunidades. Se determinó el estado nutrición de los preescolares con indicadores antropométricos y se obtuvo el IMC de las madres de estos infantes. Se aplicó una encuesta socionutricional, incluida el recordatorio de 24 horas, y complementado con la observación participante (cualitativa. Se encontró que 83% de las madres mazahuas presentaron sobrepeso u obesidad. El estado de nutrición de los preescolares con madres con obesidad presentó un porcentaje mayor de desnutrición (76%. En la variable género, se encontró que 54% de los niños con madres con obesidad tenía baja talla. Al relacionar el nivel educativo de la madre, esta variable resultó ser estadísticamente significativa (p=0.015, donde el analfabetismo está más relacionado con la desnutrición infantil que tienen madres de bajo y/o peso normal. La elevada prevalencia de hogares conformados con preescolares con desnutrición y madres con obesidad, es un síntoma más de la pobreza en zonas indígenas en México, con bajo índice de desarrollo humano.

Assessment of Response to Lithium Maintenance Treatment in Bipolar Disorder: A Consortium on Lithium Genetics (ConLiGen Report.

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Mirko Manchia

Full Text Available The assessment of response to lithium maintenance treatment in bipolar disorder (BD is complicated by variable length of treatment, unpredictable clinical course, and often inconsistent compliance. Prospective and retrospective methods of assessment of lithium response have been proposed in the literature. In this study we report the key phenotypic measures of the "Retrospective Criteria of Long-Term Treatment Response in Research Subjects with Bipolar Disorder" scale currently used in the Consortium on Lithium Genetics (ConLiGen study.Twenty-nine ConLiGen sites took part in a two-stage case-vignette rating procedure to examine inter-rater agreement [Kappa (κ] and reliability [intra-class correlation coefficient (ICC] of lithium response. Annotated first-round vignettes and rating guidelines were circulated to expert research clinicians for training purposes between the two stages. Further, we analyzed the distributional properties of the treatment response scores available for 1,308 patients using mixture modeling.Substantial and moderate agreement was shown across sites in the first and second sets of vignettes (κ = 0.66 and κ = 0.54, respectively, without significant improvement from training. However, definition of response using the A score as a quantitative trait and selecting cases with B criteria of 4 or less showed an improvement between the two stages (ICC1 = 0.71 and ICC2 = 0.75, respectively. Mixture modeling of score distribution indicated three subpopulations (full responders, partial responders, non responders.We identified two definitions of lithium response, one dichotomous and the other continuous, with moderate to substantial inter-rater agreement and reliability. Accurate phenotypic measurement of lithium response is crucial for the ongoing ConLiGen pharmacogenomic study.

A new prognostic score for AIDS-related lymphomas in the rituximab-era

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Barta, Stefan K.; Xue, Xiaonan; Wang, Dan; Lee, Jeannette Y.; Kaplan, Lawrence D.; Ribera, Josep-Maria; Oriol, Albert; Spina, Michele; Tirelli, Umberto; Boue, Francois; Wilson, Wyndham H.; Wyen, Christoph; Dunleavy, Kieron; Noy, Ariela; Sparano, Joseph A.

2014-01-01

While the International Prognostic Index is commonly used to predict outcomes in immunocompetent patients with aggressive B-cell non-Hodgkin lymphomas, HIV-infection is an important competing risk for death in patients with AIDS-related lymphomas. We investigated whether a newly created prognostic score (AIDS-related lymphoma International Prognostic Index) could better assess risk of death in patients with AIDS-related lymphomas. We randomly divided a dataset of 487 patients newly diagnosed with AIDS-related lymphomas and treated with rituximab-containing chemoimmunotherapy into a training (n=244) and validation (n=243) set. We examined the association of HIV-related and other known risk factors with overall survival in both sets independently. We defined a new score (AIDS-related lymphoma International Prognostic Index) by assigning weights to each significant predictor [age-adjusted International Prognostic Index, extranodal sites, HIV-score (composed of CD4 count, viral load, and prior history of AIDS)] with three risk categories similar to the age-adjusted International Prognostic Index (low, intermediate and high risk). We compared the prognostic value for overall survival between AIDS-related lymphoma International Prognostic Index and age-adjusted International Prognostic Index in the validation set and found that the AIDS-related lymphoma International Prognostic Index performed significantly better in predicting risk of death than the age-adjusted International Prognostic Index (P=0.004) and better discriminated risk of death between each risk category (P=0.015 vs. P=0.13). Twenty-eight percent of patients were defined as low risk by the ARL-IPI and had an estimated 5-year overall survival (OS) of 78% (52% intermediate risk, 5-year OS 60%; 20% high risk, 5-year OS 50%). PMID:25150257

Dexamethasone, Intravenous Immunoglobulin, and Rituximab Combination Immunotherapy for Pediatric Opsoclonus-Myoclonus Syndrome.

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Pranzatelli, Michael R; Tate, Elizabeth D

2017-08-01

Although pulse-dose dexamethasone is increasingly favored for treating pediatric opsoclonus-myoclonus syndrome (OMS), and multimodal immunotherapy is associated with improved clinical response, there have been no neuroimmunologic studies of dexamethasone-based multimodal disease-modifying therapy. In this observational retrospective study, 19 children with OMS (with or without associated neuroblastoma) underwent multibiomarker evaluation for neuroinflammation. Nine children of varying OMS severity, duration, and treatment status were treated empirically with pulse dexamethasone, intravenous immunoglobulin (IVIg), and rituximab combination immunotherapy (DEXIR-CI). Another 10 children on dexamethasone alone or with IVIg at initial evaluation only provided a comparison group. Motor severity (total score) was scored rater-blinded via videotapes using the validated OMS Evaluation Scale. DEXIR-CI was associated with a 69% reduction in group total score (P = 0.004) and was clinically well tolerated. Patients given the dexamethasone combination exhibited significantly lowered B cell frequencies in cerebrospinal fluid (-94%) and blood (-76%), normalizing the cerebrospinal fluid B cell percentage. The number of patients with positive inflammatory markers dropped 87% (P = 0.002) as did the number of markers. Cerebrospinal fluid oligoclonal bands were positive in four of nine pretreatment patients but zero of six post-treatment patients. In the comparison group, partial response to dexamethasone alone or with IVIg was associated with multiple positive markers for neuroinflammation despite an average of seven months of treatment. Multimechanistic dexamethasone-based combination immunotherapy increases the therapeutic armamentarium for OMS, providing a viable option for less severely affected individuals. Partial response to dexamethasone with or without IVIg is indicative of ongoing neuroinflammation and should be treated promptly and accordingly. Copyright © 2017

Terapia regenerativa con plasma rico en plaquetas en pacientes con quemaduras

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María del Carmen Franco Mora

2015-10-01

Full Text Available Se realizó un estudio comparativo, longitudinal y prospectivo de 60 adultos con quemaduras profundas, atendidos en el Hospital General docente "Dr. Juan Bruno Zayas Alfonso" de Santiago de Cuba, desde febrero de 2013 hasta igual mes de 2014, para evaluar la efectividad de la terapia regenerativa con plasma rico en plaquetas para la cicatrización de estas lesiones. La muestra fue dividida en 2 grupos de 30 integrantes cada uno: a los del primero se les aplicó plasma rico en plaquetas y a los del segundo sulfadiazina de plata. Se utilizaron las frecuencias absolutas y el porcentaje como medidas de resumen para variables cualitativos, así como la media aritmética y la desviación estándar para las cuantitativas. Con el proceder aplicado la cicatrización se completó en un tiempo menor, de manera que se demostró la efectividad de esta alternativa terapéutica en relación con el tratamiento convencional

Beneficios de la suplementación con L-carnitina en pacientes pediátricos hemodializados. Reporte de casos

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JA Martínez-Morales

2016-09-01

Full Text Available INTRODUCCIÓN: la mayoría de los pacientes pediátricos con insuficiente renal crónica desarrollan desnutrición y anemia. Para tratar esta última se administra eritropoyetina como tratamiento de elección, pero no se logra recuperar la situación nutricional del paciente, por lo que la L-carnitina es una alternativa que mejora el estado nutricional y, al mismo tiempo, disminuye la frecuencia de anemia. OBJETIVO: mejorar los parámetros bioquímicos y antropométricos después de la suplementación con L carnitina en pacientes pediátricos.  MATERIAL Y MÉTODOS: se realizó un estudio analítico y longitudinal, de una serie de casos en 25 participantes, ambos sexos, de 3 a 16 años de edad, con insuficiencia renal crónica y en tratamiento de hemodiálisis. Se les suministró L-carnitina por vía intravenosa (50 mg/ kg/sesión 30 minutos antes de terminar las sesiones de hemodiálisis, durante tres meses (36 sesiones. Antes y después de la maniobra se compararon algunos indicadores bioquímicos (hemoglobina, albumina, colesterol, triglicéridos, creatinina y antropométricos. Se realizó una comparación con T de Student y por proporciones (casos que mejoraron después de maniobra y la reducción del riesgo absoluto. RESULTADOS: la edad promedio de los casos fue 12.4 años (rango de 3 a 16 años. Al comparar los casos con T de Student se obtuvo una mejora significativa con la suplementación para el peso seco (p=0.004; índice de masa corporal (p=0.04; albúmina (p=0.02 y colesterol (p=0.003. Con el cálculo por proporciones de los casos que mejoraron con la maniobra se observó la reducción del riesgo atribuible en un rango de 12 a 68% de todas las variables de interés (hemoglobina, albúmina, colesterol, triglicéridos, peso seco e índice de masa corporal. CONCLUSIONES: la suplementación con L-carnitina intravenosa (50 mg/kg/sesión 30 minutos antes de terminar cada sesión de hemodiálisis, durante tres meses

Neurofibromatosis tipo I con manifestaciones en el periodonto y lengua: presentación de un caso Type I neurofibromatosis with periodontal and lingual manifestations: a case report

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M.C. Negreiros Lyrio

2008-06-01

Full Text Available La enfermedad de Von Recklinghausen o Neurofibromatosis Tipo I (NF1 es una condición autosómica dominante que presenta una variada expresión clínica, con manifestaciones que van desde manchas tipo café con leche en piel a severas complicaciones estéticas y funcionales afectando los tejidos óseos y nerviosos. Las manifestaciones orales de la NF1 son comunes, afectando aproximadamente al 72% de los pacientes. Presentamos un caso de NF1 con lesiones neurofibromatosas afectando al reborde alveolar inferior y lengua, con indicación de excisión quirúrgica debido a la dificultad de higiene local.Von Recklinghausen’s disease, or type I neurofibromatosis (NF-1, is an autosomal dominant condition with a varied clinical expression. Disease manifestations may range from café au lait spots of the skin to severe cosmetic and functional complications that affect bone and nervous tissues. Oral manifestations of NF-1 are common, affecting approximately 72% of patients. We report a case of NF-1 with neurofibromatous lesions of the lower alveolar bridge and tongue. Resection was indicated due to the difficulty of maintaining oral hygiene.

Desensibilización con aspirina en un paciente con intolerancia a antiinflamatorios no esteroides Aspirin desensitization in a patient who exhibit intolerance to non-steroidal anti-inflammatories

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Mirta Álvarez Castelló

2011-12-01

Full Text Available El ácido acetilsalicílico o aspirina es uno de los medicamentos más utilizados a nivel mundial. Los pacientes con enfermedad coronaria requieren tratamientos prolongados con este medicamento, el cual se les niega a aquellos con historias de reacciones adversas a este. Se recoge en la literatura internacional el uso de terapias de desensibilización en pacientes con intolerancia a los antiinflamatorios no esteroides con diferentes protocolos, con resultados satisfactorios. En este trabajo se describe la primera desensibilización con aspirina realizada a un paciente en el Hospital Universitario «Calixto García» y el protocolo de actuación utilizado. No se encontró otro caso en la bibliografía nacional. El paciente actualmente ingiere 125 mg diarios sin reacciones adversas. Se considera que la desensibilización con aspirina es una opción terapéutica efectiva en aquellos pacientes con intolerancia a esta y con una afección que justifique este proceder.Aspirine is one of the most widely used drugs worldwide. The patients suffering from heart diseases require long-term treatment with this drug, which is banned to those having adverse reactions. The international literature collects information on the use of desensitization therapies in patients who do not exhibit tolerance to this medicine, following different protocols with satisfactory results. This paper described the first aspirin desensitization procedure, which was performed at «Calixto García» university hospital, and the performance protocol. There was not any other case of this type reported in the national literature. The patient can presently take 125 mg of aspirin daily without suffering adverse events. It was considered that the desensitization process is an effective therapeutic action for patients who are aspirin sensitive and who have specific diseases that warrant this procedure.

Reporte de familias con neurofibromatosis y otras enfermedades genéticas

OpenAIRE

Orraca Castillo, Miladys; Licourt Otero, Deysi; Sánchez Álvarez de La Campa, Ana Isabel

2011-01-01

La neurofibromatosis tipo 1, es una enfermedad genética que primariamente afecta el desarrollo y crecimiento celular del sistema nervioso, clínicamente se caracteriza por máculas café con leche, neurofibromas, pecas en regiones no expuestas al sol, nódulos de Lisch, lesiones óseas y glioma óptico. En el presente trabajo se describen dos familias, en las cuales algunos individuos padecen esta enfermedad y otros miembros de la misma familia muestran una diferente enfermedad genética. La coexist...

Retrospective analysis of bendamustine and rituximab use in indolent and mantle cell non-Hodgkin lymphoma based on initial starting dose.

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Bond, David A; Huang, Ying; Ruppert, Amy S; Walker, Alison R; Dotson, Emily K; Roddy, Julianna; Blum, Kristie A; Christian, Beth A

2017-07-01

The initial dose of bendamustine, an alkylating agent used in treating indolent lymphoma (iNHL) and mantle cell lymphoma, is variable in clinical practice. 134 patients treated with bendamustine and rituximab were evaluated for starting dosage, patient characteristics, toxicities, and clinical outcome. The starting dosage ranged from 50 to 90 mg/m 2 . Lower starting dosage (<90 mg/m 2 ) was associated with relapsed disease, increased age and worse performance status (PS), histologic subtype other than follicular lymphoma, baseline renal impairment, and cytopenias. No significant difference was observed in toxicities between patients treated with 90 mg/m 2 compared with lower doses. The starting dose of 90 mg/m 2 was associated with a higher complete response rate (56% vs. 29%) and longer progression free survival (PFS) (39.5 months vs. 19.7 months). However, in a multivariable model, the higher starting dose was not associated with longer PFS in those with similar age, histology, PS, and number of prior therapies.

Glaucoma maligno en paciente con cirugía previa de catarata traumática e implante valvular: reporte de caso

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Juan Carlos Serna-Ojeda

2015-07-01

Full Text Available El glaucoma maligno es un glaucoma secundario asociado con un bloqueo ciliar y dirección equivocada del flujo del humor acuoso. Se presenta el caso de un paciente masculino de 19 años con antecedente de explosión de filtro metálico en ojo derecho. Se encuentra con una presión intraocular de 52 mmHg y cristalino luxado a cámara anterior. Se inicia terapia máxima para glaucoma y se realiza facoemulsificación con posterior colocación de válvula de Ahmed, y 3 semanas después de la cirugía presenta hallazgos clínicos compatibles con glaucoma maligno. Se presenta el seguimiento del paciente y los estudios de imagen indicados

Calidad de vida, satisfacción con el tratamiento y bienestar emocional en pacientes con diabetes LADA

OpenAIRE

Granado Casas, Minerva

2014-01-01

Introducción: La calidad de vida, satisfacción con el tratamiento y bienestar emocional en pacientes con diabetes mellitus están relacionados con el control metabólico, las complicaciones y algunas variables socioeconómicas. Actualmente, no existe ningún estudio científico que analice la calidad de vida, satisfacción con el tratamiento y bienestar emocional en pacientes con diabetes LADA. Objetivos: Los objetivos principales fueron conocer la calidad de vida, satisfacción con el tratamient...

Dgroup: DG02612 [KEGG MEDICUS

Lifescience Database Archive (English)

Full Text Available DG02612 Chemical ... DGroup Rituximab ... D02994 ... Rituximab (USAN/INN); Rituximab (gene...tical recombination) (JAN); Rituximab (genetical recombination) [Rituximab biosimilar 1] (JAN) ... ATC code:

Procarbazine-induced hepatotoxicity: case report and review of the literature.

Science.gov (United States)

Fesler, Mark J; Becker-Koepke, Stephanie; Di Bisceglie, Adrian M; Petruska, Paul J

2010-05-01

Procarbazine hydrochloride is an oral alkylating agent primarily used as a component of chemotherapy regimens for Hodgkin's lymphoma, as well as in regimens for primary central nervous system lymphoma and high-grade gliomas. Although the prescribing information for procarbazine lists hepatic dysfunction as a potential adverse reaction, we found only one published report with a probable link between procarbazine and liver injury. We describe a 65-year-old man who developed liver injury due to procarbazine during salvage chemotherapy for non-Hodgkin's lymphoma. The patient had no preexisting liver disease, his lymphoma was without hepatic involvement, and no liver injury developed after initial chemotherapy with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone). Due to relapse of his non-Hodgkin's lymphoma, salvage chemotherapy with C-MOPP-R (cyclophosphamide, vincristine, procarbazine, prednisone, and rituximab) was administered, and the patient developed fever and aminotransferase level elevation during the second cycle. After discontinuation of all drug therapy, exclusion of other potential etiologies, and resolution of hepatic injury, the patient was rechallenged with procarbazine and again experienced fever with aminotransferase level elevation. His aminotransferase levels promptly returned to normal after discontinuation of procarbazine, and he experienced no further evidence of liver disease. Use of validated scoring systems of drug-induced liver injury indicated a definitive association between the patient's hepatic injury and procarbazine. Based on our experience with this patient, periodic assessment of hepatic function, as suggested in the package insert, is recommended in patients receiving procarbazine.

Assessment of Response to Lithium Maintenance Treatment in Bipolar Disorder: A Consortium on Lithium Genetics (ConLiGen) Report

Science.gov (United States)

Manchia, Mirko; Adli, Mazda; Akula, Nirmala; Ardau, Raffaella; Aubry, Jean-Michel; Backlund, Lena; Banzato, Claudio EM.; Baune, Bernhard T.; Bellivier, Frank; Bengesser, Susanne; Biernacka, Joanna M.; Brichant-Petitjean, Clara; Bui, Elise; Calkin, Cynthia V.; Cheng, Andrew Tai Ann; Chillotti, Caterina; Cichon, Sven; Clark, Scott; Czerski, Piotr M.; Dantas, Clarissa; Zompo, Maria Del; DePaulo, J. Raymond; Detera-Wadleigh, Sevilla D.; Etain, Bruno; Falkai, Peter; Frisén, Louise; Frye, Mark A.; Fullerton, Jan; Gard, Sébastien; Garnham, Julie; Goes, Fernando S.; Grof, Paul; Gruber, Oliver; Hashimoto, Ryota; Hauser, Joanna; Heilbronner, Urs; Hoban, Rebecca; Hou, Liping; Jamain, Stéphane; Kahn, Jean-Pierre; Kassem, Layla; Kato, Tadafumi; Kelsoe, John R.; Kittel-Schneider, Sarah; Kliwicki, Sebastian; Kuo, Po-Hsiu; Kusumi, Ichiro; Laje, Gonzalo; Lavebratt, Catharina; Leboyer, Marion; Leckband, Susan G.; López Jaramillo, Carlos A.; Maj, Mario; Malafosse, Alain; Martinsson, Lina; Masui, Takuya; Mitchell, Philip B.; Mondimore, Frank; Monteleone, Palmiero; Nallet, Audrey; Neuner, Maria; Novák, Tomás; O’Donovan, Claire; Ösby, Urban; Ozaki, Norio; Perlis, Roy H.; Pfennig, Andrea; Potash, James B.; Reich-Erkelenz, Daniela; Reif, Andreas; Reininghaus, Eva; Richardson, Sara; Rouleau, Guy A.; Rybakowski, Janusz K.; Schalling, Martin; Schofield, Peter R.; Schubert, Oliver K.; Schweizer, Barbara; Seemüller, Florian; Grigoroiu-Serbanescu, Maria; Severino, Giovanni; Seymour, Lisa R.; Slaney, Claire; Smoller, Jordan W.; Squassina, Alessio; Stamm, Thomas; Steele, Jo; Stopkova, Pavla; Tighe, Sarah K.; Tortorella, Alfonso; Turecki, Gustavo; Wray, Naomi R.; Wright, Adam; Zandi, Peter P.; Zilles, David; Bauer, Michael; Rietschel, Marcella; McMahon, Francis J.

2013-01-01

Objective The assessment of response to lithium maintenance treatment in bipolar disorder (BD) is complicated by variable length of treatment, unpredictable clinical course, and often inconsistent compliance. Prospective and retrospective methods of assessment of lithium response have been proposed in the literature. In this study we report the key phenotypic measures of the “Retrospective Criteria of Long-Term Treatment Response in Research Subjects with Bipolar Disorder” scale currently used in the Consortium on Lithium Genetics (ConLiGen) study. Materials and Methods Twenty-nine ConLiGen sites took part in a two-stage case-vignette rating procedure to examine inter-rater agreement [Kappa (κ)] and reliability [intra-class correlation coefficient (ICC)] of lithium response. Annotated first-round vignettes and rating guidelines were circulated to expert research clinicians for training purposes between the two stages. Further, we analyzed the distributional properties of the treatment response scores available for 1,308 patients using mixture modeling. Results Substantial and moderate agreement was shown across sites in the first and second sets of vignettes (κ = 0.66 and κ = 0.54, respectively), without significant improvement from training. However, definition of response using the A score as a quantitative trait and selecting cases with B criteria of 4 or less showed an improvement between the two stages (ICC1 = 0.71 and ICC2 = 0.75, respectively). Mixture modeling of score distribution indicated three subpopulations (full responders, partial responders, non responders). Conclusions We identified two definitions of lithium response, one dichotomous and the other continuous, with moderate to substantial inter-rater agreement and reliability. Accurate phenotypic measurement of lithium response is crucial for the ongoing ConLiGen pharmacogenomic study. PMID:23840348

Mastopexia con prótesis: técnica triplanar con colgajo en cola de pez para mamas con pobre calidad de cobertura

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M. Berrocal-Revueltas

2013-12-01

Full Text Available La mastopexia con implantes de silicona, es uno de los procedimientos más frecuentes en la práctica diaria en Cirugía Plástica. Sin embargo, la pobre calidad de la cobertura de las mamas, relacionada con piel estriada, escaso tejido subcutáneo y pérdida del parénquima mamario secundarios a la lactancia prolongada y a la pérdida masiva de peso, son causa del incremento progresivo de resultados insatisfactorios a medio y largo plazo que han sido evaluados, analizados y discutidos por los especialistas. Los resultados insatisfactorios más frecuentes en mastopexia con implantes en posición retromuscular son: doble contorno mamario, asimetrías y desplazamiento de los implantes. Los objetivos del presente estudio son: describir el nuevo método triplanar como alternativa útil para lograr mejores resultados en pacientes con mala calidad de cobertura y analizar los resultados obtenidos con el mismo. Realizamos un estudio observacional, descriptivo, prospectivo, en un grupo de 268 pacientes con diagnóstico de ptosis mamaria con hipotrofia y mala calidad de cobertura por piel estriada, escaso tejido celular subcutáneo y pérdida del parénquima mamario, secundarios a lactancia prolongada y pérdida masiva de peso, entre otros, a las que se les practicó mamoplastia de aumento con implantes de silicona mediante la aplicación del método triplanar descrito por la autora, entre enero del 2004 y enero del 2013 en el Hospital de Bocagrande de Cartagena, Colombia. El diseño de la técnica se basa en los principios de cicatriz vertical descrita por Lassus o Lejour o mediante cicatriz en "J", descrita por la autora. El método triplanar se basa en tres planos de cobertura del implante. Plano I: submuscular, para cubrir los dos tercios superiores del implante. Plano II: colgajo dermoglandular con dos prolongaciones distales triangulares de tejido adiposo, en forma de pez, para cubrir el tercio inferior del implante y el borde libre del m

Characterization of a Novel Humanized Anti-CD20 Antibody with Potent Anti-Tumor Activity against Non-Hodgkin's Lymphoma

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Haifeng Zhang

2013-09-01

Full Text Available Background: Rituximab, a mouse Fab and human Fc chimeric antibody, has been widely used to treat Non-Hodgkin's lymphoma (NHL. However, only 48% of patients respond to the treatment and complete response rate is below 10%. Also, immunogenicity was reported in 17-20% patients receiving the treatment, making it unsuitable for long term diseases such as autoimmune disorders. It has been a hot research field to “humanize” rituximab toward improved efficacy and reduced immunogenicity. Methods: In this study, an advanced antibody humanization technology was applied to the sequence of the anti-CD20 antibody 2B8, its sequence of which was based on the original murine monoclonal antibody of rituximab in Roche. The complementarity-determining regions (CDRs of the humanized antibodies were further optimized through computer-aided molecular dock. Results: Five novel humanized anti-CD20 antibodies 1-5(1635, 1534, 3637, 1634 and 1536 were generated and their immunogenicity was significantly decreased when compared to rituximab. The novel humanized anti-CD20 antibodies 1-5 retained the binding activity of their murine counterpart, as demonstrated by the fluorescence-activated cell-sorting analysis (FACS. When compared to rituximab, the humanized antibodies still have the similar properties on both complement-dependent cytotoxicity (CDC and antibody-dependent cell-mediated cytotoxicity (ADCC. Furthermore, its anti-tumor efficacy in xenograft model is comparable to that of rituximab. Conclusion: The humanized anti-CD20 antibodies 1-5 have lower immunogenicity than rituximab. And at the same time, they still retain the anti-tumor effect both in vitro and vivo.

Estudio comparativo del efecto del cepillado con una crema dental con propóleos rojos y de un gel con clorofila

OpenAIRE

Estela Gispert Abreu; Elena Cantillo Estrada; Aracelys Rivero López; Berta Oramas Rodríguez

1998-01-01

Se analiza comparativamente el efecto de un gel dental de clorofila y de una crema dental con propóleos rojos sobre varios parámetros relacionados con la caries dental, en escolares que se cepillaron durante 21 días con dichos productos. Se obtuvieron resultados favorables principalmente en la disminución del grado de infección por Streptococcus mutans y la elevación de la capacidad individual de remineralización; salvo en este último no hubo diferencias estadísticamente significativas.Author...

Posttransplant Lymphoproliferative Disorder After Clinical Islet Transplantation: Report of the First Two Cases.

Science.gov (United States)

Peters, A; Olateju, T; Deschenes, J; Shankarnarayan, S H; Chua, N; Shapiro, A M J; Senior, P

2017-09-01

We report the first two cases of posttransplant lymphoproliferative disorder (PTLD) in recipients of islet transplants worldwide. First, a 44-year-old recipient of three islet infusions developed PTLD 80 months after his initial transplantation, presenting with abdominal pain and diffuse terminal ileum thickening on imaging. He was treated with surgical excision, reduction of immunosuppression, and rituximab. Seven months later, he developed central nervous system PTLD, presenting with vertigo and diplopia; immunosuppression was discontinued, resulting in graft loss, and he was given high-dose methotrexate and underwent consolidative autologous stem cell transplantation. He remains in remission 37 months after the initial diagnosis. Second, a 58-year-old female recipient of two islet infusions developed PTLD 24 months after initial islet infusion, presenting with pancytopenia secondary to extensive bone marrow involvement. Immunosuppression was discontinued, resulting in graft loss, and she received rituximab and chemotherapy, achieving complete remission. Both patients were monomorphic B cell PTLD subtype by histology and negative for Epstein-Barr virus in tissue or blood. These cases document the first occurrences of this rare complication in islet transplantation, likely secondary to prolonged, intensive immunosuppression, and highlight the varying clinical manifestations of PTLD. Further studies are needed to determine incidence rate and risk factors in islet transplantation. © 2017 The American Society of Transplantation and the American Society of Transplant Surgeons.

EMBARAZO EXITOSO EN PACIENTE CON DISGENESIA GONADAL PURA

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Claudia Ortiz A.

2010-12-01

Full Text Available

Resumen

Objetivo: Reporte de un caso de embarazo exitoso en una paciente con disgenesia gonadal pura.
Diseño de estudio: Informe de caso.
Lugar: Centro de Fertilidad y Reproducción Fundación Santa Fe de Bogotá (REPROTEC.
Paciente: Una paciente con disgenesia gonadal 46,XY confi rmada.
Intervención: Gonadectomía por laparoscopia, fertilización in vitro con donación de oocitos, transferencia de embriones en blastocisto (2 y parto por cesárMea.
Resultado principal: Embarazo exitoso y nacido vivo.
Conclusiones: Las pacientes con disgenesia gonadal pura 46,XY; tienen como opción de fertilidad, la donación de ovocitos y transferencia de embriones con adecuadas tasas de embarazos exitosos.

Palabras clave: síndrome de Swyer, disgenesia gonadal pura, fertilización in vitro

SUCCESSFUL PREGNANCY IN A PATIENT WITH PURE GONADAL DYSGENESIS

Abstract

Sexual differentiation is a complex process, that begins from conception with determination of genetic sex and from sixth week, gonadal differentiation; any alteration in any of the tracts can cause conditions where there is discordance between phenotype and genotype, that are called alterations in sexual development. Swyers syndrome and the syndrome of androgen insensitivity share the characteristics of a female phenotype with 46, XY karyotype.

Key words: Swyer Syndrome, Pure Gonadal Dysgenesis, in vitro fertilization.

Oligodendroglioma in a patient with AIDS: case report and review of the literature Oligodendroglioma en un paciente con sida: reporte de caso y revisión de la literatura

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Marcelo E. Corti

2004-08-01

Full Text Available In the last years, new techniques of neuroimages and histopathological methods have been added to the management of cerebral mass lesions in patients with AIDS. Stereotactic biopsy is necessary when after 14 days of empirical treatment for Toxoplasma gondii encephalitis there is no clinical or neuroradiologic improvement. We report a woman with AIDS who developed a single focal brain lesion on the right frontal lobe. She presented a long history of headache and seizures. After two weeks of empirical treatment for toxoplasma encephalitis without response, a magnetic resonance image with spectroscopy was performed and showed a tumoral pattern with a choline peak, diminished of N-acetyl-aspartate and presence of lactate. A stereotactic biopsy was performed. Histopathological diagnosis was a diffuse oligodendroglioma type A. A microsurgical resection of the tumor was carried out and antiretroviral treatment was started. To date she is in good clinical condition, with undetectable plasma viral load and CD4 T cell count > 200 cell/uL.En los últimos años, las nuevas técnicas de neuroimágenes y diversos métodos de diagnóstico histopatológico se han agregado al manejo clínico de las lesiones de masa cerebral ocupante en los pacientes con sida. La biopsia estereotáxica es necesaria cuando, luego de dos semanas de tratamiento empírico para toxoplasmosis cerebral, no se comprueba mejoría clínica ni neurorradiológica. Presentamos una paciente con sida que desarrolló una lesión cerebral a nivel del lóbulo frontal derecho. Como antecedente refirió una larga historia de cefalea y convulsiones. La resonancia nuclear magnética con espectroscopia de voxel único ubicado a nivel de la lesión mostró un patrón de lesión tumoral con pico de colina, déficit de N-acetil-aspartato y presencia de ácido láctico. La biopsia estereotáxica y el estudio histopatológico permitieron arribar al diagnóstico de oligodendroglioma difuso de tipo A. Se le

Myelofibrosis and acquired hemophilia A: a case report.

Science.gov (United States)

Wrobel, Marie; Comio, Emilie; Gay, Valerie; Baroudi, Noureddine; Meyer, Pascal; Chuniaud-Louche, Christine; Hacini, Maya; Pica, Gian Matteo

2016-05-07

Myelofibrosis and acquired hemophilia A is a rare association. To the best of our knowledge only one case of myelofibrosis and acquired hemophilia A has been previously described. A 66-year-old Caucasian man diagnosed with myelofibrosis evolving in acute myeloid leukemia was referred to us for postoperative bleeding. Hemostatic studies showed prolonged activated partial thromboplastin time, decreased factor VIII coagulation, and a high factor VIII inhibitor titer; these findings led to a diagnosis of acquired hemophilia A for which he was treated with methylprednisolone and recombinant activated factor VII on admission. Due to a lack of response he was subsequently treated with rituximab combined with activated prothrombin complex concentrates. Furthermore, he received azacytidine to treat the underlying hematological malignancies. Immunosuppressive rituximab therapy resolved acquired hemophilia A with marked efficacy. Rapid and accurate diagnosis, effective hemostatic therapy, and timely treatment for underlying disease are important in the management of acquired hemophilia A secondary to hematological malignancy.

Time course of bone mineral density changes during 4-year rituximab therapy in postmenopausal women with rheumatoid arthritis

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T. A. Raskina

2015-01-01

Full Text Available Objective: to estimate the time course of bone mineral density (BMD changes during 4-year rituximab (RTM therapy in postmenopausal women with rheumatoid arthritis (RA.Subjects and methods. Seventy-nine postmenopausal women with a valid diagnosis of RA were followed up. According to the basic therapy option, all the patients were allocated into two groups: 1 44 patients who received combination therapy with RTM and methotrexate (MT; 2 35 patients who had MT monotherapy. BMD was estimated by dual-energy X-ray absorptiometry using an Excell XR-46 stationary dualenergy X-ray bone densitometer (Norland, USA.Results. There was a statistically significant increase in femoral neck BMD and T score as compared to the baseline values in the RTM group after 3 years of follow-up. The MT monotherapy group showed no statistically significant densitometric changes in the femoral neck. The similar positive BMD changes were observed 4 years following RTM and MT therapy.Conclusion. Following 2 therapy cycles, femoral neck BMD parameters were noted to be stabilized in the patients with RA. After 3 therapy cycles, there was a positive densitometric change that remained by the fourth therapy cycle.

Investigando con personas con dificultades de aprendizaje

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Borja González Luna

2013-12-01

Full Text Available El artículo muestra los orígenes de lo que Walmsley (2008 denomina «investigación inclusiva». Para comprender qué se entiende por investigación inclusiva tenemos que remontarnos a los debates epistemológicos sobre las metodologías cuantitativas y cualitativas, acontecidos en la década de los 90, en torno a la revista Disability & Society. A partir de una síntesis de dichos debates, focalizados en el ámbito de la «discapacidad intelectual y del desarrollo», se exponen dos estrategias de colaboración con dicha población: a una aproximación etnográfica (de trabajo grupal, y b una aproximación biográfica (de trabajo individual. A continuación se esboza un posible diseño de trabajo de campo que intenta superar el paradigma cualitativo «clásico» con el objetivo de incluir a dicho colectivo más allá del rol de «sujetos de la investigación». Para finalizar se recoge el debate sobre la accesibilidad de los resultados de la investigación a los participantes en dichas investigaciones, y con ello la necesaria innovación en el ámbito de las «devoluciones» de los resultados, cuando se trata de incluir a personas que presentan limitaciones para la comprensión del lenguaje abstracto oral y/o escrito.

Gastric diffuse large B cell lymphoma presenting as para neoplastic cerebellar degeneration: Case report and review of literature

International Nuclear Information System (INIS)

Lakshmaiah, K.C.; Viveka, B.K.; Kumar, N.A.; Saini, M.L.; Sinha, S.; Saini, K.S.

2013-01-01

Para neoplastic cerebellar degeneration (PCD) is a type of para neoplastic neurological disorder (PND) that is associated with many solid tumors, Hodgkins lymphoma (HL) and very rarely with non-Hodgkin lymphoma (NHL). We report a case of PCD associated with gastric diffuse large B-cell lymphoma (DLBCL) in a patient who presented with acute onset of giddiness and double vision and had complete remission of the gastric lesion and marked improvement of cerebellar syndrome with rituximab-based combination chemotherapy. A brief review of the literature is also presented.

MODELADO CON REDES DE PETRI E IMPLEMENTACIÓN CON GRAFCET DE UN SISTEMA DE MANUFACTURA FLEXIBLE CON PROCESOS CONCURRENTES Y RECURSOS COMPARTIDOS

OpenAIRE

Johanna Stella Castellanos Arias; Leonardo Enrique Solaque Guzmán

2010-01-01

En este trabajo, se presenta el modelado de un Sistema de Manufactura Flexible (SMF), con procesos concurrentes y recursos compartidos mediante Sistemas a Eventos Discretos (SED), específicamente Redes de Petri (RdP), y GRAFCET. El SMF se plantea como un modelo hipotético que se modela con una RdP con el objeto de identificar su dinámica y hallar la secuencia óptima de funcionamiento del sistema. Se desarrolló un modelo matemático que permite estimar el vector de tiempo acumulado de un proces...

Perspectiva espiritual de la mujer con cáncer

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Milena Alexandra Galvis-López

2011-01-01

Full Text Available Objetivo: comparar la perspectiva espiritual de las mujeres diagnosticadas con cáncer propio de su género (seno, útero, ovarios y de las mujeres diagnosticadas con otros tipos de cáncer. Método: diseño cuantitativo de tipo descriptivo comparativo, de corte transversal. Se empleó una encuesta sociodemográfica para caracterizar la población y la Escala de perspectiva espiritual de Pamela Reed, a la cual se le realizó el análisis de confiabilidad que reportó un alfa de Cronbach de 0,799 en el grupo 1 y 0,763 en el grupo 2. La muestra incluyó a 100 mujeres que se encuentran en tratamiento contra el cáncer. Resultados: la perspectiva espiritual de las mujeres con cáncer propio de su género es moderada al igual que la de las mujeres con otros tipos de cáncer; al hacer la comparación de estos dos grupos no se encontró evidencia estadística que demostrara una diferencia significativa. Discusión: los resultados de este estudio aportan nuevos elementos para el cuidado de las mujeres con enfermedad oncológica y señalan que una perspectiva espiritual moderada puede ser un potencial para su cuidado integral, en el que la enfermera reconozca sus objetivos en el cuidado de la mujer como un ser total, más que el tipo de cáncer que tiene.

con mala calidad de vida

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Agustín Martín-Rodríguez

2007-01-01

Full Text Available En este estudio ex post facto se ha analizado si los familiares de pacientes con mala calidad de vida presentan diferencias en las variables clínicas de personalidad y relaciones familiares en función de que el paciente haya estado o no ingresado en una Unidad de Cuidados Intensivos. Seleccionamos dos grupos: 29 familiares de pacientes traumatizados graves transcurridos cuatro años de su ingreso en una UCI de Traumatología y con mala calidad de vida (debido a secuelas físicas y/o psicológicas tras el ingreso, tales como traumatismos craneoencefálicos, politraumatismos y tetraplejias traumáticas y 32 familiares de pacientes con mala calidad de vida con cuatro años de evolución de su enfermedad física (hipertensión, diabetes, artritis reumatoide y síndrome de intestino irritable que no han estado ingresados en la UCI. Para alcanzar nuestro objetivo empleamos una Encuesta Psicosocial y los siguientes instrumentos: Cuestionario de Análisis Clínico, Escala de Clima Social en la Familia y Escala de Adaptación Psicosocial de la Enfermedad. Los resultados mostraron que los familiares de pacientes con mala calidad de vida que estuvieron ingresados en la UCI hace cuatro años, presentan diferencias significativas en las variables agitación y expresividad comparados con los familiares de pacientes con mala calidad de vida que no han estado ingresados en la UCI.

Estandarización de una prueba de ELISA para detectar anticuerpos IgE en pacientes con equinococosis quistica y su utilidad en el diagnóstico y seguimiento de pacientes tratados con albendazol: reporte preliminar

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Herman Vildózola

2012-01-01

Full Text Available Objetivos: Determinar las diluciones y concentraciones optimas de una prueba de ELISA para detectar anticuerpos IgE, así como su sensibilidad, espécificidad y valor predictivo en pacientes con equinococosis quistica. Analizar si los niveles de anticuerpos IgE especificos se correlacionan con la respuesta al tratamiento médico con albendazol en un periodo mayor a un año de finalizado el tratamiento. Diseño: Estudio cuasiexperimental con grupo control. Institución: Instituto de Medicina Tropical Daniel A. Carrión, Facultad de Medicina, UNMSM, Lima, Perú. Material de estudio: Prueba de ELISA para anticuerpo IgE. Intervenciones: Estandarizacion de la prueba de ELISA para anticuerpo IgE y diseño preexperimento con preprueba y posprueba en un solo grupo, para evaluar su valor en el diagnóstico y seguimiento postratamiento de pacientes con quiste hidatidico hepatico tratados con albendazol. Para la estandarizacion de la prueba de ELISA, se utilizó suero de cinco pacientes con diagnóstico clínico de equinococosis quistica, y la sensibilidad y especificidad de la prueba se usó suero de 30 pacientes aparentemente sanos. Para determinar las reacciones cruzadas, se utilizó 16 muestras de suero de pacientes con otras helmintiasis (ascariasis, strongiloidiasis, toxocariosis, trichuriasis, himenolepiasis, cisticercosis y teniasis. Para el diagnóstico y seguimiento postratamiento de equinocococosis quística, se utilizó el suero de 17 pacientes. Principales medidas de resultados: Sensibilidad y especificidad de prueba estandarizada de ELISA para detectar anticuerpos IgE. Resultados: La prueba estandarizada de ELISA para detectar anticuerpos IgE tuvo una sensibilidad de 95,6% y una especificidad de 100%. En los pacientes con quiste hidatídico hepático considerados curados, uniformemente disminuyeron los niveles de anticuerpo tipo IgE hasta la negativización. Se obtuvo elevación de los niveles de IgE en los pacientes que presentaron

Calidad de vida relacionada con la salud del niño y del adolescente con obesidad

OpenAIRE

Hurtado-Valenzuela, Jaime Gabriel; Álvarez-Hernández, Gerardo

2014-01-01

Objetivo Estimar la calidad de vida relacionada con la salud (CVRS) en un grupo de niños y adolescentes con obesidad de la ciudad de Hermosillo, Sonora, México. Métodos Se realizó un estudio transversal utilizando el cuestionario PedsQL® para comparar la CVRS de 200 niños y adolescentes con obesidad al igual que a sus padres, con dos grupos de control, uno de la comunidad (n=400) y otro grupo de usuarios (n=200) del Hospital Infantil del Estado de Sonora. Las diferencias en la CVRS fueron eva...

Pulpotomía con electrocauterio en pacientes con hemofilia A

OpenAIRE

Carbonell Rodriguez, Rosario

2017-01-01

Rehabilita la salud oral de un niños con Hemofilia A, empleando el Electrocauterio como una alternativa en la terapia pulpar, específicamente en la pulpotomía, para lo cual se realiza un minucioso examen clínico y anamnesis, que respaldados con exámenes complementarios, permite determinar el plan de tratamiento. La rehabilitación integral se llevó a cabo, previo consentimiento informado del padre, en sala de operaciones bajo anestesia general, debido a la condición sistémica del niño. Incl...

Intervención con menores con adicciones desde Proyecto Hombre

OpenAIRE

Pardo-Esteban, Belén; Escalza-González, Amaia

2015-01-01

En el citado seminario informaremos del programa de atención y prevención de las toxicomanías y otras adicciones, llevado a cabo por la Asociación Proyecto hombre. A continuación, trataremos la formación en adicciones y toxicomanía con los estudiantes, mediante charla, cuestionarios sobre conocimientos básicos en prevención de toxicomanía en menores y los diferentes programas de intervención posibles aducados a los perfiles de los usuarios. Terminaremos con un debate sobre los temas tra...

NARRATIVAS CONVERSACIONALES CON FAMILIAS Y DOCENTES DE NIÑOS Y NIÑAS CON DISCAPACIDAD: UN APORTE METODOLÓGICO

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NORA ANETH PAVA-RIPOLL

2015-01-01

Full Text Available Se presentan algunas ventajas y limitaciones de las narrativas conversacionales como estrategia de investigación para el trabajo con familias y docentes de niños con discapacidad. La narración realizada por muchas voces, como sucede en una conversación, privilegia la relación y el discurso entre las personas como fuente de construcción consensuada de significados. La interacción triádica entre familia, inclusión educativa y salud orientó los encuentros conversacionales con padres, acudientes y profesores de estos niños en la ciudad de Manizales (Colombia. Los participantes conformaron equipos conversacionales y equipos reflexivos y conversaron sobre preguntas propuestas, previamente elaboradas. Con este ejercicio investigativo se resalta el valor interaccional de esta estrategia desde tres ámbitos: entre los par ticipantes, con el investigador y con el contexto situacional. Se argumenta que la reflexividad está más relacionada con el hacer que con el ser y el sentir de las personas, las cuales no necesariamente se transforman en la narrativa...

Drug: D02994 [KEGG MEDICUS

Lifescience Database Archive (English)

Full Text Available D02994 Drug Rituximab (USAN/INN); Rituximab (genetical recombination) (JAN); Ritux...imab (genetical recombination) [Rituximab biosimilar 1] (JAN); Rituxan (TN) ... Therapeutic category: 429

MODELADO CON REDES DE PETRI E IMPLEMENTACIÓN CON GRAFCET DE UN SISTEMA DE MANUFACTURA FLEXIBLE CON PROCESOS CONCURRENTES Y RECURSOS COMPARTIDOS

Directory of Open Access Journals (Sweden)

Johanna Stella Castellanos Arias

2010-01-01

Full Text Available En este trabajo, se presenta el modelado de un Sistema de Manufactura Flexible (SMF, con procesos concurrentes y recursos compartidos mediante Sistemas a Eventos Discretos (SED, específicamente Redes de Petri (RdP, y GRAFCET. El SMF se plantea como un modelo hipotético que se modela con una RdP con el objeto de identificar su dinámica y hallar la secuencia óptima de funcionamiento del sistema. Se desarrolló un modelo matemático que permite estimar el vector de tiempo acumulado de un proceso modelado mediante una RdP, el cual constituye la base para hallar la mejor secuencia posible del sistema modelado. Por último, se realizó una implementación en el Laboratorio de Automatización de la Universidad Militar Nueva Granada, que simula el funcionamiento del SMF modelado por un montaje electrohidroneumático controlado con GRAFCET mediante PLC.

Relación del perfil salival con el grado de inmunosupresión en pacientes infectados con VIH con y sin tratamiento antirretroviral

OpenAIRE

Vera Cruz, Moisés; Cornejo Salaza, José; Chiyong, Teresa Evaristo; Arevalo Abanto, Jorge A.; Villanueva Vílchez, Hugo G.

2014-01-01

El objetivo del estudio fue evaluar el perfil salival de pacientes con infección por VIH con y sin Tratamiento Antirretroviral de Gran Actividad (TARGA), por medio de la evaluación de los síntomas de hipofunción salival (Xerostomía, Disgeusia, Disfagia y Susceptibilidad de desarrollar úlceras orales), la Tasa de Flujo salival no estimulado, el pH salival y la viscosidad salival; estableciendo su relación con el Grado de Inmunosupresión, evaluado por medio del Recuento de Linfocitos CD4/μl. Se...

A Patient with Non-Hodgkin Lymphoma and Nonspecific Interstitial Pneumonia during Ibrutinib Therapy

OpenAIRE

Jungmann, Sven; Ludwig, Wolf-Dieter; Schönfeld, Nicolas; Blum, Torsten-Gerriet; Großwendt, Claudia; Boch, Christian; Rehbock, Beate; Griff, Sergej; Schmittel, Alexander; Bauer, Torsten T.

2017-01-01

We present a 74-year-old male with nonspecific interstitial pneumonia (NSIP) during treatment with ibrutinib for mantle cell lymphoma. Previously, the patient had received six cycles of bendamustine and rituximab and six cycles of R-CHOP, followed by rituximab maintenance therapy. Respiratory tract complications of ibrutinib other than infectious pneumonia have not been mentioned in larger trials, but individual case reports hinted to a possible association with the development of pneumonitis...

Catastrophic antiphospholipid syndrome. Case report and literature review

Science.gov (United States)

del Carpio-Orantes, Luis; Martínez-Anaya, Chantall Citlally; Bonilla-Casas, Elías

2017-01-01

The present document is the report of a case of a very rare clinical entity, which presents with acute multiorganic failure after a thrombotic storm related to antiphospholipid antibodies, the so-called catastrophic antiphospholipid syndrome, which began as a recurrent picture of mesenteric thrombosis, with a previous history of venous insufficiency and distal ulcers probably associated with an unidentified antiphospholipid; deserving management in intensive care and the consultation by the world expert, Dr. Ricard Cervera who confirmed the diagnosis and recommend treating as such entity, the patient's evolution was satisfactory so far. Final recommendations for diagnosis and current treatment options such as rituximab or eculizumab are made. The present case was added to the international registry that currently houses around 500 cases worldwide (International CAPS Registry). Copyright: © 2017 SecretarÍa de Salud

SATISFACCIÓN CON EL TRATAMIENTO EN PACIENTES DE ATENCIÓN PRIMARIA CON ARTROSIS

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Carmen Llanos Val Jiménez

2017-01-01

Full Text Available Fundamentos: Al igual que en otros problemas crónicos, en el abor - daje del paciente con artrosis se tiende a un modelo de toma de decisiones compartidas, en el que el punto de vista del paciente debe ser considerado en la elección del tratamiento. El objetivo de este trabajo fue evaluar la sa - tisfacción con el tratamiento en pacientes diagnosticados de osteoartrosis y comprobar si existen diferencias entre diferentes opciones farmacológicas, así como determinar si existe asociación con el estado funcional y las carac - terísticas clínicas y sociodemográficas. Métodos: Se realizó un estudio observacional transversal en una muestra de 487 pacientes seleccionados mediante muestreo consecutivo. La variable principal fue el nivel de satisfacción con el tratamiento (cuestionario ARTS. El estado funcional de los pacientes fue evaluado mediante la escala WO - MAC. Otras variables fueron: características del tratamiento, adherencia te - rapéutica, eventos adversos, y variables clínicas y sociodemográficas. Resultados: En el cuestionario ARTS los pacientes, en un rango entre 28 y 87, obtuvieron una puntuación media de 65,3 (DE: 9,9. La puntuación no fue significativamente diferente en consumidores de 1, 2 o más fármacos. Entre quienes consumían un solo fármaco, no hubo diferencias entre los di - ferentes tipos de fármacos. En el estado funcional se obtuvo una puntuación media de 30,2 puntos (DE: 20,8 y se observó una débil correlación negativa con el nivel de satisfacción (r= - 0,252; p<0,001. Mediante regresión lineal múltiple, se observó mayor puntuación en la escala ARTS (p<0,05 en pa - cientes con menor puntuación en la escala WOMAC, mayor edad y ausencia de eventos adversos. Conclusión : En pacientes con osteoartritis se observa un nivel mode - rado de satisfacción con el tratamiento farmacológico, condicionado por su situación funcional, sus características sociodemográficas y por la presencia de eventos

Hidroxilación de fenol con catalizadores ZSM-5 modificado con cobre

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César Augusto Caro

2005-01-01

Full Text Available Se sintetizaron varios catalizadores Cu-ZSM-5 con diferentes relaciones Si/Al y Si/Cu. Usando metilamina o hidróxido de sodio como agente mineralizante. Los catalizadores se caracterizaron por DRX, IR, análisis BET, UV-VIS y análisis elemental. El desempeño catalítico de los catalizadores sintetizados se evaluó en la hidroxilación de fenol con H2O2. Se encontró que la relación catecol (CAT/(hidroquinona (HQ + p-benzoquinona (PBQ aumentó con el contenido de agua, presentó un máximo cuando la relación en peso de agua/fenol fue de 53/1 y se favoreció a altas temperaturas, con el aumento del contenido de aluminio o con la disminución en el contenido de catalizador. El contenido de cobre no fue un factor determinante para la conversión ni para la selectividad en la hidroxilación de fenol. La producción de la p-benzoquinona (PBQ, producto de oxidación de la hidroquinona, fue mínimo cuando se usaron las siguientes condiciones: 80 ºC, fenol: 1 mmol, relación molar fenol/H2O2 de 3/1, catalizador: 20 mg, agua: 5 g, tiempo de reacción: 4 h.

ESTUDIO DE LA DIGESTION HUMANA CON ALUMNOS CON DIFICULTADES DE APRENDIZAJE

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Mª Begoña Carretero Gómez

2009-01-01

Full Text Available En esta experiencia se han seleccionado una serie de actividades relacionadas con la digestión con el fin de lograr una reestructuración de ideas y cambios conceptuales, y así con la conseguir que el alumnado aprenda a construir sus propios conocimientos acerca de cómo y donde se dan los procesos de digestión necesarios para la nutrición del organismo. El trabajo se ha llevado a cabo con alumnos de 3º de Educación Secundaria Obligatoria, pertenecientesal programa de diversificación curricular. Hemos querido hacer la ciencia más cercana para que comprendan que algunos procesos tienen su explicación científica y que la ciencia forma parte de nuestro día a día, fomentando el interés del estudiante así como su implicación en el proceso de enseñanza-aprendizaje. Por ello hemos trabajado a base de pequeñas investigaciones, donde es el alumno el que marca su ritmo de trabajo, investiga y hace sus aportaciones. Han aprendido a trabajar de una forma meticulosa donde el rigor esfundamental, contagiándose del afán investigador de manera que al realizar las experiencias se han aproximado al trabajo científico a la vez que aclaran y reestructuran conocimientos.

Sobredentadura sobre implantes en paciente con múltiples caries. Reporte de caso.

OpenAIRE

Rengifo Alarcón, Carlos Alberto; Vicente Zamudio, Eduardo Gregorio; Balarezo Razzeto, José Antonio; Matta Morales, Carlos

2014-01-01

Hasta hace poco tiempo el tratamiento de pacientes desdentados totales era mediante la instalación de prótesis que iban a ser soportadas por las estructuras remanentes de los maxilares sobrela mucosa y la retención, estabilidad y soporte dependían de la cantidad de hueso remanente, forma de los maxilares, calidad de saliva presente, todos éstos influenciados por la capacidadpsicomotriz del paciente. Con la introducción de los implantes dentales y más aun los implantes endo-óseos se ha revoluc...

Falla cardiaca asociada con el uso de imatinib mesilato: Reporte de un caso Heart failure associated to imatinib mesylate use: Case report

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Clara Saldarriaga

2008-12-01

Full Text Available La cardiotoxicidad por medicamentos es un evento cada vez más frecuente en la práctica clínica diaria. Inhibidores de la proteína de fusión Brc/Abl como el imatinib mesilato, son una nueva herramienta para el tratamiento de algunas neoplasias hematológicas, en especial de la leucemia mieloide crónica. Sin embargo, en la literatura se reporta desarrollo de cardiotoxicidad a causa de este medicamento. Se presenta el caso de una mujer joven con corazón de estructura sana quien desarrolla cardiotoxicidad por imatinib pocas semanas después de iniciarlo.Cardiotoxicity due to drugs has become a frequent event in the daily clinical practice. Fusion protein Brc/Abl inhibitors such as imatinib mesylate constitute a new tool for the treatment of some hematogical neoplasias, especially chronic myeloid leukemia. Nevertheless, there have been reports in the literature regarding imatinib mesylate toxicity. We present the case of a young woman with a structurally healthy heart who developed cardiotoxicity with imatinib few weeks after its initiation.

Las relaciones con los públicos y su reflejo en las memorias de Responsabilidad Social. Public Relations and Corporate Social Responsibility reports

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isabel Ruiz Mora

2012-12-01

Full Text Available ResumenEl diálogo y las relaciones con los públicos se postulan como unos de los principales retos de la Responsabilidad Social en las organizaciones. Los públicos se convierten en elementos protagonistas de gran parte de las acciones de las empresas y de sus políticas de RSE y la sociedad, comienza a incluir a la Responsabilidad Social en sus demandas hacia las organizaciones. Por tanto, un enfoque de la RSE basado en la gestión de las relaciones con los públicos se hace necesario.Nuestra investigación tiene por objeto el estudio de la relación que se establece entre la responsabilidad social y la gestión de las relaciones con los públicos en las empresas y cómo éstas, transmiten y reflejan dicha relación en sus memorias de Responsabilidad Social o Sostenibilidad. El objetivo principal será conocer cómo gestionan las grandes empresas españolas las relaciones con sus stakeholders. El diseño metodológico se centra en el análisis de contenido aplicado a las actividades que las grandes empresas españolas recogen en sus memorias de Responsabilidad Social relacionadas con sus grupos de interés.Los principales resultados nos acercan a organizaciones que gestionan sus relaciones con los públicos, dando un mayor protagonismo a accionistas, inversores y empleados; que emplean herramientas de comunicación tradicionales principalmente, aunque comienzan a hacerse eco de nuevos canales de diálogo. Como novedad, destacamos la aparición de nuevos grupos de interés y herramientas de comunicación como el microblogging o las redes sociales.AbstractDialogue and the management of public relations are postulated as ones of the major challenges related to CSR in the companies. Publics are becoming one of the best features of many of the actions carried out by organizations and their CSR policies and stakeholders are including CSR in their demands. An approach to CSR from Public Relation is needed.Our research aims to study the relationship

Esporotricosis cutánea diseminada con compromiso articular en una mujer con diabetes tipo 2

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Sendy Solorzano

Full Text Available La esporotricosis diseminada es una presentación infrecuente de esta micosis. Aunque ha sido descrita en sujetos inmunocompetentes, con frecuencia existe compromiso de la inmunidad mediada por células T. Reportamos el caso de una mujer con diabetes tipo 2 no controlada que desarrolló esporotricosis cutánea diseminada. El curso de la enfermedad presentó varias complicaciones que incluyeron hepatitis secundaria a itraconazol y artritis de la rodilla con cultivo positivo para Sporothrix schenckii durante el tratamiento con solución saturada de ioduro de potasio. La discusión del caso incluye aspectos de la patogénesis de la esporotricosis diseminada y el manejo de la infección y sus complicaciones.

Adenocarcinoma de recto y ano en paciente con enfermedad de Crohn tratado con infliximab Adenocarcinoma of the rectum and anus in a patient with Crohn´s disease treated with infliximab

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J. Egea Valenzuela

2010-08-01

Full Text Available In the present paper, we report the case of a patient with long-standing Crohn´s disease and multiple complications that, after receiving treatment with infliximab, was diagnosed with an adenocarcinoma of the rectum and anus that required radical surgery, later presenting multiple metastases. In the discussion, characteristics and major risk factors for colorectal cancer in patients with inflammatory bowel disease will be largely reviewed, and current studies will be analyzed in connection with the appearance of neoplasms in patients being treated with biologics.Presentamos el caso de un paciente con enfermedad de Crohn de larga evolución y con múltiples complicaciones de su enfermedad que, tras recibir tratamiento con infliximab, es diagnosticado de un adenocarcinoma de recto y ano que precisa cirugía radical, presentando posteriormente metástasis múltiples. Se repasarán durante la discusión las características y los factores de riesgo más importantes del cáncer colorrectal en pacientes con enfermedad inflamatoria intestinal, y se analizarán los trabajos existentes hasta la fecha en relación con la aparición de neoplasias en pacientes tratados con fármacos biológicos.

Efficacy of Remission-Induction Regimens for ANCA-Associated Vasculitis

Science.gov (United States)

Specks, Ulrich; Merkel, Peter A.; Seo, Philip; Spiera, Robert; Langford, Carol A.; Hoffman, Gary S.; Kallenberg, Cees G.M.; St. Clair, E. William; Fessler, Barri J.; Ding, Linna; Viviano, Lisa; Tchao, Nadia K.; Phippard, Deborah J.; Asare, Adam L.; Lim, Noha; Ikle, David; Jepson, Brett; Brunetta, Paul; Allen, Nancy B.; Fervenza, Fernando C.; Geetha, Duvuru; Keogh, Karina; Kissin, Eugene Y.; Monach, Paul A.; Peikert, Tobias; Stegeman, Coen; Ytterberg, Steven R.; Mueller, Mark; Sejismundo, Lourdes P.; Mieras, Kathleen; Stone, John H.

2018-01-01

Background The 18-month efficacy of a single course of rituximab as compared with conventional immunosuppression with cyclophosphamide followed by azathioprine in patients with severe (organ-threatening) antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis is unknown. Methods In a multicenter, randomized, double-blind, double-dummy, noninferiority trial, we compared rituximab (375 mg per square meter of body-surface area administered once a week for 4 weeks) followed by placebo with cyclophosphamide administered for 3 to 6 months followed by azathioprine for 12 to 15 months. The primary outcome measure was complete remission of disease by 6 months, with the remission maintained through 18 months. Results A total of 197 patients were enrolled. As reported previously, 64% of the patients in the rituximab group, as compared with 53% of the patients in the cyclophosphamide–azathioprine group, had a complete remission by 6 months. At 12 and 18 months, 48% and 39%, respectively, of the patients in the rituximab group had maintained the complete remissions, as compared with 39% and 33%, respectively, in the comparison group. Rituximab met the prespecified criteria for noninferiority (P<0.001, with a noninferiority margin of 20%). There was no significant difference between the groups in any efficacy measure, including the duration of complete remission and the frequency or severity of relapses. Among the 101 patients who had relapsing disease at baseline, rituximab was superior to conventional immunosuppression at 6 months (P = 0.01) and at 12 months (P = 0.009) but not at 18 months (P = 0.06), at which time most patients in the rituximab group had reconstituted B cells. There was no significant between-group difference in adverse events. Conclusions In patients with severe ANCA-associated vasculitis, a single course of rituximab was as effective as continuous conventional immunosuppressive therapy for the induction and maintenance of remissions over the

Enfermedad de Carrión grave complicada con leptospirosis aguda: reporte de un caso

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Anderson Huerta

Full Text Available Se reporta el caso de un adulto varón de 56 años, procedente de Sihuas (Ancash que acude al Hospital Nacional Dos de Mayo con cuadro clínico caracterizado por un síndrome ictérico febril anemizante, en cuya evolución tórpida de solo tres días de hospitalizado presenta anemia severa (Hb: 11,8 a 6,7 g/dL así como mialgias generalizadas asociadas a un empeoramiento brusco de la ictericia correlacionada con elevación de bilirrubinas (BT: 3,2 a 19,6 mg/dL a predominio directo y deterioro general del paciente; por ello, se realizó la investigación microbiológica donde se encontró frotis y cultivo positivo para Bartonella bacilliformis, posteriormente, la serología (microaglutinación resultó positiva para Lesptospira serovar Pomona. El paciente recibe tratamiento antibiótico específico (ceftriaxona y ciprofloxacino, se le transfunde dos paquetes globulares, mejora clínicamente y es dado de alta

Efectos del tratamiento con litio sobre las funciones neurosicológicas de pacientes con trastorno bipolar de tipo I

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Anabel Martínez Aran

2008-11-01

Full Text Available OBJETIVO: determinar si el tratamiento continuo con litio influye en el desempeño cognitivo de un grupo de pacientes eutímicos con trastorno afectivo bipolar I. MÉTODO: se evaluó el desempeño cognitivo usando pruebas neurosicológicas de atención, memoria y función ejecutiva en 20 pacientes eutímicos con trastorno afectivo bipolar I que no tomaban medicación, 20 pacientes eutímicos con trastorno afectivo bipolar I quienes continuaban regularmente el tratamiento con carbonato de litio, y un tercer grupo de 20 pacientes control. RESULTADOS: no se encontraron diferencias estadísticamente significativas entre los dos grupos de pacientes con trastorno afectivo bipolar. Sin embargo, al compararlos con el grupo control, su desempeño en términos de memoria verbal, viso-verbal y asociación semántica medida fue menor. DISCUSIÓN: los pacientes con trastorno afectivo bipolar I muestran deficiencias en términos de memoria verbal y viso-verbal que no pueden ser atribuidos al tratamiento regular con carbonato de litio. Por el contrario, estas deficiencias podrían ser consideradas como características de rasgo de este trastorno.

TAFRO Syndrome Associated with EBV and Successful Triple Therapy Treatment: Case Report and Review of the Literature

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Malorie Simons

2016-01-01

Full Text Available TAFRO syndrome is a rare constellation of symptoms: thrombocytopenia, anasarca, reticulin fibrosis of the bone marrow, renal dysfunction, and organomegaly. Its pathogenesis involves an excessive and inappropriate cytokine storm, most notably from IL-6, causing multiorgan failure; however, its etiology is undetermined. Starting in 2012, TAFRO syndrome was first identified in Japan as an atypical variant of Castleman’s disease. Previous reports include various different treatment protocols with inconsistent survival outcomes. Here we report the first known American, EBV positive but HIV and HHV-8 negative, male with TAFRO syndrome. He was successfully treated with an unusual three-drug regimen including tocilizumab, etoposide, and rituximab. We review the literature of TAFRO syndrome, discuss its possible viral etiology, and propose an original treatment regimen.

Acne polimorfo: tratamiento con Implacen

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Rubén Pérez Armas

1995-06-01

Full Text Available Se realiza el estudio de 40 pacientes con acné polimorfo, los que fueron atendidos en la Consulta de Dermatología del Hospital Provincial Clinicoquirúrgico Docente "Celia Sánchez Manduley", en el período comprendido de enero de 1988 a diciembre de 1989. Se revisa la literatura médica sobre los diversos métodos y medicamentos utilizados en la terapéutica de esta dermatosis. Se describe el esquema de tratamiento empleado con implacén en 30 pacientes; los 10 restantes se trataron con placebo; se compara dicho esquema con los tradicionales y se observan mejores resultados con nuestro estudio. Se destaca la ausencia de recaídas, así como el resultado del tratamiento de acuerdo con el sexo.A study was performed in 40 patients presenting with polymorphic acne who were attended in the Dermatology Department of "Celia Sánchez Manduley" Clinicosurgical and Teaching Hospital from January, 1988 to December, 1989. A review of the literature was made seeking for the different methods and drugs used for the treatment of this dermatosis. The treatment schedule with the use of implacen in 30 patients is described. Such therapeutic schedule was compared with traditional ones and better results were observed with the use of implacen. The fact that there were no relapses is highlighted, as well as the result of treatment according to sex.

Reducción de color con cloruro de magnesio en soluciones con colorantes comerciales

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Mercedes Lucero Chávez

2017-01-01

Full Text Available Se experimentó con diferentes concentraciones de cloruro de magnesio (MgCl2 como coagulante para reducir el color en soluciones con colorantes comerciales: negro, azul y café. Los parámetros analizados fueron pH, color, demanda química de oxígeno ( dqo y sólidos suspendidos totales (sst de acuerdo con las Normas Mexicanas. Como prueba complementaria se agregó carbón activado a las muestras para reducir el color residual después de la coagulación-floculación. La reducción de los valores de color y dqo fue mayor cuando se adicionó más cantidad de MgCl2 (1.8 g/L. Los porcentajes de reducción fueron ≥90% para el color y >50% para la dqo. Los sst aumentaron con la adición de MgCl2. El carbón activado eliminó el color residual.

Aprende Ajedrez con Rey - Parte 2

OpenAIRE

ESTÉVEZ MONTERO, RAÚL; Lloret Mauri, Jaime

2016-01-01

Es una pieza audiovisual creada con el objeto de atraer la atención de los niños de muy corta edad con el ajedrez y familiarizarlos con todas sus piezas y movimientos. Es una animación dirigida a un público infantil presentada por dibujos animados en 2D, en la que se ha intentado respetar en todo momento el argot de la comunidad ajedredística. En este video se presenta la segunda parte. Estévez Montero, R.; Lloret Mauri, J. (2016). Aprende Ajedrez con Rey - Parte 2. http://hdl.handle.net/1...

Aprende Ajedrez con Rey - Parte 1

OpenAIRE

ESTÉVEZ MONTERO, RAÚL; Lloret Mauri, Jaime

2016-01-01

Es una pieza audiovisual creada con el objeto de atraer la atención de los niños de muy corta edad con el ajedrez y familiarizarlos con todas sus piezas y movimientos. Es una animación dirigida a un público infantil presentada por dibujos animados en 2D, en la que se ha intentado respetar en todo momento el argot de la comunidad ajedredística. En este video se presenta la primera parte. Estévez Montero, R.; Lloret Mauri, J. (2016). Aprende Ajedrez con Rey - Parte 1. http://hdl.handle.net/1...

Waldenström makroglobulinemili hastada rituksimab tedavisi sonrası gelişen gizli hepatit B reaktivasyonu

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Vedat Aslan

2012-12-01

Full Text Available The anti-CD20 monoclonal antibody rituximab has beenused extensively in the treatment of B-cell lymphoma.Several studies reported hepatitis B virus (HBV reactivationafter rituximab. The majority of these cases havebeen described in chronic carriers of HBV, whereas reactivationin occult hepatitis B virus (OHBV carriers mayoccur.The presented case with the diagnosis of Waldenström’smacroglobulinemia was HBsAg negative and anti HBcIgGpositive before chemotherapy. The patient was started onCVP (cyclophosphamide, vincristine, prednisolone chemotherapy.However, no clinical or laboratory responsewas obtained and the patient was considered unresponsiveto three cycles of CVP therapy. Therefore R-CHOP(rituximab, cyclophosphamide, adriamycin, vincristineand prednisolone was planned as the second therapy.Laboratory work-up after the first cycle of R-CHOP therapyrevealed an aspartate aminotransferase (AST levelof 267 U/L and alanine aminotransferase (ALT level of318 U/L. HBsAg and anti HBcIgG were positive and HBVDNA was 56400 IU/ml. Lamivudin 100 mg/day was started.Four weeks after the initiation of lamivudin therapy,ALT and AST levels returned to normal. Currently, the patienthas received the fourth cycle of R-CHOP therapy.ALT and AST levels continue to be in normal range. Thiscondition was considered to be the reactivation of OHBVfollowing rituximab.The aim of this case presentation is to call attention toHBV reactivation possibility in cases taking immunosupressivemedications like Rituximab. J Clin Exp Invest2012; 3(4: 541-544Key words: Waldenström’s macroglobulinemia, rituximab,occult HBV infection

Prevalencia de bruxismo de vigilia evaluado por auto-reporte en relación con estrés, ansiedad y depresión

OpenAIRE

Ordóñez-Plaza, Miriam Patricia; Villavicencio-Caparó, Ébingen

2016-01-01

Objetivos: El objetivo de este estudio fue relacionar el estrés, la ansiedad y la depresión con la prevalencia del bruxismo probable de vigilia en los estudiantes universitarios de la Facultad de Odontología de la Universidad de Cuenca. Materiales y métodos: se realizó un diseño de casos y controles, donde se evaluaron en total 284 pacientes, se utilizó un cuestionario de auto reporte más la examinación clínica para determinar el bruxismo “probable” de vigilia y se aplicó la escala DASS-21 pa...

Prevalencia de bruxismo de vigilia evaluado por auto-reporte en relación con estrés, ansiedad y depresión

OpenAIRE

Ordóñez-Plaza, Miriam Patricia; Villavicencio-Caparó, Ébingen; Alvarado-Jiménez, Omar Ricardo; Vanegas-Avecillas, María Elizabeth

2016-01-01

Objetivos: El objetivo de este estudio fue relacionar el estrés, la ansiedad y la depresión con la prevalencia del bruxismo probable de vigilia en los estudiantes universitarios de la Facultad de Odontología de la Universidad de Cuenca. Materiales y métodos: se realizó un diseño  de casos y controles, donde se evaluaron en total 284 pacientes, se utilizó un cuestionario de auto reporte más la examinación clínica para determinar el bruxismo “probable” de vigilia y se aplicó la escala DASS-21 p...

Videojuego con Realidad Virtual

OpenAIRE

González Mora, César

2017-01-01

El objetivo del proyecto es el desarrollo de un videojuego deportivo que utilice realidad mixta. El videojuego se podrá utilizar con dispositivos de tipo cardboard, y utilizará realidad aumentada para la interacción del jugador con el videojuego. En el desarrollo se utilizará el motor Unity para conseguir una aplicación multiplataforma, y la librería Vuforia para implementar realidad mixta.

Factores psicosociales relacionados con la rehospitalización de pacientes con psicosis orgánica

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Cortés-Padilla María Teresa

2001-01-01

Full Text Available Objetivo. Conocer los factores psicosociales relacionados con la frecuente rehospitalización de pacientes con psicosis orgánica. Material y métodos. Estudio de tipo observacional descriptivo, de corte transversal. La muestra estuvo formada por 33 pacientes del Hospital Psiquiátrico Guillermo Dávila, con Unidad de Medicina Familiar Número 10 del Instituto Mexicano del Seguro Social de la Ciudad de México, con psicosis orgánica y quienes durante los años de 1993-1994 presentaron más de dos rehospitalizaciones. Instrumentos: Entrevista grabada, o muestra de conversación de cinco minutos, para la emoción expresada (EE, cuestionarios mixtos para la Concepción de Enfermedad y la Relación médico-paciente. La validez y confiabilidad de los datos se establecieron con las pruebas de Kappa y Alpha de Cronbach y se efectuó análisis estadístico descriptivo e inferencial. Resultados. El 60.9% de los familiares presentan alto nivel de EE, es decir, expresan crítica, hostilidad o sobreinvolucramiento emocional; el 64.3% de los sujetos de la muestra conviven más de 35 horas a la semana con familiares que presentan Alta EE. Conclusiones. Altos niveles de EE estuvieron asociados con los frecuentes reingresos a hospitalización. Existe mayor conocimiento de las características de la enfermedad por parte del familiar que del paciente. La relación médico-paciente es satisfactoria pero no forma conciencia de enfermedad ni propicia apego al tratamiento terapeútico. El texto completo en inglés de este artículo está disponible en: http://www.insp.mx/salud/index.html

Intravenous immunoglobulins and rituximab therapy for severe transplant glomerulopathy in chronic antibody-mediated rejection: a pilot study.

Science.gov (United States)

Bachelet, Thomas; Nodimar, Celine; Taupin, Jean-Luc; Lepreux, Sebastien; Moreau, Karine; Morel, Delphine; Guidicelli, Gwendaline; Couzi, Lionel; Merville, Pierre

2015-05-01

Outcome of patients with transplant glomerulopathy (TG) is poor. Using B-cell targeting molecules represent a rational strategy to treat TG during chronic antibody-mediated rejection. In this pilot study, 21 patients with this diagnosis received four doses of intravenous immunoglobulins and two doses of rituximab (IVIG/RTX group). They were retrospectively compared with a untreated control group of 10 patients. At 24 months post-biopsy, graft survival was similar and poor between the treated and the untreated group, 47% vs. 40%, respectively, p = 0.69. This absence of response of IVIG/RTX treatment was observed, regardless the phenotype of TG. Baseline estimated glomerular filtration rate (eGFR) and decline in eGFR during the first six months after the treatment were risk factors associated with 24-month graft survival. The IVIG/RTX therapy had a modest effect on the kinetics of donor-specific alloantibodies at M24, compared to the untreated group, not associated with an improvement in graft survival. The mean number of adverse events per patient was higher in the IVIG/RTX group than in the control group (p = 0.03). Taken together, IVIG/RTX treatment for severe TG during chronic antibody-mediated rejection does not seem to change the natural history of TG and is associated with a high incidence of adverse events. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Análisis probabilista con caminata al azar del número de personas viviendo con VIH mundialmente

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Javier Oswaldo Rodríguez-Velásquez

2018-01-01

Full Text Available Introducción: El estudio de la dinámica anual de la epidemia de VIH a partir de la caminata al azar ha mostrado ser de utilidad para llevar este fenómeno altamente variable a un comportamiento predecible Objetivo: Predecir el comportamiento de la dinámica del número de personas viviendo con VIH mediante la caminata al azar probabilista. Metodología: Se analizaron los valores anuales de personas que a nivel global viven con VIH desde el año 1990 hasta el 2009, a partir de los espacios de probabilidad generados con la caminata al azar probabilista, para posteriormente desarrollar la predicción del valor anual de personas viviendo con VIH para los años 2010, 2011 y 2012. Resultados: Se predijeron los valores anuales de personas viviendo con VIH con un porcentaje de acierto de 98,95% para el año 2010, de 98,82% para el año 2011 y de 98,99% para la predicción realizada para el año 2012. Conclusiones: Se establecieron órdenes matemáticos a partir de la caminata al azar probabilista, estableciendo predicciones prácticamente deterministas del número de personas viviendo con VIH, lo que podría ser útil para las decisiones en Salud Pública y para la evaluación de intervenciones.

Rituximab for the therapy of systemic sclerosis: a series of 10 cases in a single center.

Science.gov (United States)

Vilela, Verônica Silva; Maretti, Giselle Baptista; Gama, Lívia Marques da Silva; Costa, Claudia Henrique da; Rufino, Rogério Lopes; Levy, Roger A

Systemic sclerosis (SSc) is a chronic autoimmune disease with a high morbidity and mortality. Although cyclophosphamide is effective for severe and refractory cases, there is demand for new treatments. The biological treatment with B-cell depletion with rituximab (RTX) has demonstrated efficacy for this demand in open-label studies. This study was conducted with the aim to retrospectively evaluate all patients who used RTX for the treatment of SSc in our center. We retrospectively evaluated medical records of all patients with SSc who used RTX to treat this disease from January 2009 to January 2015. Systemic, cutaneous, and pulmonary involvement data and laboratory results before and six months after the first infusion of RTX were collected. Ten patients received treatment during the study period and were included in this series. All patients had a diffuse form of the disease. Five patients suffered from an early (duration of disease shorter or equal to four years), rapidly progressive disease, and another five received RTX at late stages of the disease. In both groups of patients, stabilization of the pulmonary picture was observed, with a fall in the skin score in those patients with early forms of the disease. Similar to findings in previous studies, RTX was effective in treating early and rapidly progressive forms of SSc. We also found that patients with long-term illness may benefit from the treatment. Copyright © 2016. Published by Elsevier Editora Ltda.

Fuerza manual de adultos con discapacidad intelectual

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Ruth Cabeza Ruiz

2017-09-01

Full Text Available Objetivo. Presentar una descripción de la fuerza de prensión manual de hombres y mujeres con discapacidad intelectual (DI y comparar los resultados con valores de referencia de otras personas con y sin discapacidad intelectual. Método. El presente trabajo es un estudio transversal observacional, financiado por la Fundación SAMU, en el que se evaluaron a 122 personas con DI (86 hombres y 36 mujeres durante el desarrollo de unas jornadas de carácter recreativo en las que participaron varias asociaciones de atención a este colectivo. La batería de test utilizada fue el Alpaha-Fit Test Battery for Adults. Resultados. Se presentan los resultados relacionados con las variables de fuerza del miembro superior (Hand Grip Strength por grupos de edad (20-24, 25- 29, 30-34, 35-39, 40-44, 45-49, 50-54, 55-59 años. Los datos muestran valores que oscilan desde los 31 kg en los hombres más jóvenes con DI hasta los 13.3 kg del grupo más maduro de mujeres. Estos hallazgos son similares a los valores de referencia de población con DI española. Sin embargo, son muy inferiores a los obtenidos por la población sin discapacidad de la misma edad. Conclusión. Los resultados evidencian el menor rendimiento de las personas con DI en pruebas de fuerza de prensión manual por lo que se hace evidente la necesidad de llevar a cabo programas de ejercicio físico o deporte con las personas con DI.

Prevalencia de Neospora caninum y DVB en una finca con problemas reproductivos en Sopó (Cundinamarca

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John Fredy García-Chaparro

2015-04-01

Full Text Available La investigación tuvo como objetivo determinar la prevalencia de Neospora caninum y del virus de la diarrea viral bovina (DVB en bovinos de una finca con problemas reproductivos, en el municipio de Sopó (Cundinamarca, y su relación con la presentación de abortos. Se tomaron muestras de suero sanguíneo de 397 animales de alta producción lechera y con antecedentes reproductivos, seleccionados al azar.Se utilizó la inmunofluoresencia indirecta para la N. caninum, y seroneutralización para DVB, y los procedimientos se realizaron en el Laboratorio de Enfermedades Infecciosas de la Universidad de Parma (Italia. Se encontró una prevalencia de 10.37% para DVB con respecto a 21.26% para N. caninum, y estadísticamente no hubo relación directa con respecto a los problemas reproductivos. De acuerdo con los resultados obtenidos, se reportó mayor presencia significativa de N. caninum con relación a la de DVB en el hato lechero objeto de estudio.

Sistemas integrados con Arduino

OpenAIRE

EL YAKOUTI, MOHAMMED

2017-01-01

Design of a robot prototype remotely controllable from Bluetooth using Arduino. Control and testing of sensors and events interacting with Arduino and Bluetooth. Diseño de un prototipo de robot controlable remotamente con Bluetooth utilizando Arduino. Control y verificación de los sensores y eventos que interactúan mediante el Arduino y el Bluetooth. El Yakouti, M. (2017). Sistemas integrados con Arduino. http://hdl.handle.net/10251/89274. TFGM

Response to rituximab-based therapy and risk factor analysis in Epstein Barr Virus-related lymphoproliferative disorder after hematopoietic stem cell transplant in children and adults: a study from the Infectious Diseases Working Party of the European Group for Blood and Marrow Transplantation.

Science.gov (United States)

Styczynski, Jan; Gil, Lidia; Tridello, Gloria; Ljungman, Per; Donnelly, J Peter; van der Velden, Walter; Omar, Hamdy; Martino, Rodrigo; Halkes, Constantijn; Faraci, Maura; Theunissen, Koen; Kalwak, Krzysztof; Hubacek, Petr; Sica, Simona; Nozzoli, Chiara; Fagioli, Franca; Matthes, Susanne; Diaz, Miguel A; Migliavacca, Maddalena; Balduzzi, Adriana; Tomaszewska, Agnieszka; Camara, Rafael de la; van Biezen, Anja; Hoek, Jennifer; Iacobelli, Simona; Einsele, Hermann; Cesaro, Simone

2013-09-01

 The objective of this analysis was to investigate prognostic factors that influence the outcome of Epstein-Barr virus (EBV)-related posttransplant lymphoproliferative disorder (PTLD) after a rituximab-based treatment in the allogeneic hematopoietic stem cell transplant (HSCT) setting.  A total of 4466 allogeneic HSCTs performed between 1999 and 2011 in 19 European Group for Blood and Marrow Transplantation centers were retrospectively analyzed for PTLD, either biopsy-proven or probable disease.  One hundred forty-four cases of PTLD were identified, indicating an overall EBV-related PTLD frequency of 3.22%, ranging from 1.16% for matched-family donor, 2.86% for mismatched family donor, 3.97% in matched unrelated donors, and 11.24% in mismatched unrelated donor recipients. In total, 69.4% patients survived PTLD. Multivariable analysis showed that a poor response of PTLD to rituximab was associated with an age ≥30 years, involvement of extralymphoid tissue, acute GVHD, and a lack of reduction of immunosuppression upon PTLD diagnosis. In the prognostic model, the PTLD mortality increased with the increasing number of factors: 0-1, 2, or 3 factors being associated with mortality of 7%, 37%, and 72%, respectively (P disease, and acute graft-vs-host disease predicted poor outcome.

fertilizada con diferentes abonos

Directory of Open Access Journals (Sweden)

Jorge Alberto Elizondo-Salazar

2007-01-01

Full Text Available Producción y calidad de la biomasa de morera (Morus alba fertilizada con diferentes abonos. Se llevó a cabo un experimento en la Estación Experimental “Alfredo Volio Mata” de la Universidad de Costa Rica con el fi n de evaluar la aplicación de 150 kg de N/ha/año proveniente de dos abonos orgánicos: lombriabono y compostaje; y de un fertilizante químico, sobre la producción y calidad de la biomasa de morera. El periodo experimental comprendió un ciclo de 12 meses, iniciando en julio del 2003 y fi nalizando en julio del 2004. Se utilizó una plantación de morera de 12 años de establecida con una densidad de siembra de 27.777 plantas/ ha. Se empleó un diseño de bloques completos al azar con cuatro tratamientos: dos abonos orgánicos, nitrato de amonio (33,5% N y un control. Las plantas se podaron a 0,6 m sobre el nivel del suelo al inicio del ensayo. Durante el periodo experimental, las plantas fueron podadas consecutivamente cada 90 días. Las hojas y los tallos fueron separados y analizados para determinar el contenido de materia seca y proteína cruda. La producción de materia seca fue 23% superior y el contenido de proteína cruda fue signifi cativamente mayor con el nitrógeno químico, mientras que el contenido de materia seca fue menor. No se encontraron diferencias signifi cativas entre el tratamiento control y los tratamientos orgánicos.

Estudio observacional prospectivo con insulina detemir en pacientes con diabetes mellitus tipo 2 mal controlados que inician por primer vez tratamiento con insulina (estudio SOLVE

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Domingo Orozco-Beltrán

2016-02-01

Conclusiones: En esta cohorte de pacientes con diabetes mellitus tipo 2 recientemente insulinizados, la insulina detemir (una vez al día mejoró el control glucémico, con baja incidencia de hipoglucemia y una reducción significativa del peso.

Eficacia del tratamiento tópico con Vimang® en pacientes con estomatitis subprótesis

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Laritza Coureaux Rojas

2013-10-01

Full Text Available Se efectuó un ensayo clínico terapéutico controlado de fase III en 120 pacientes con estomatitis subprótesis, atendidos en la Clínica Estomatológica Provincial Docente "Mártires del Moncada" de Santiago de Cuba, desde junio de 2010 hasta mayo de 2011, con vistas a evaluar la eficacia del tratamiento tópico con té de Vimang® en dichos pacientes. Se conformaron 2 grupos de 60 integrantes cada uno (de estudio y de control. Los primeros fueron tratados con enjuagatorios fríos de dicho té 4 veces al día y los segundos con el mismo tratamiento más vitaminas. Se utilizaron el porcentaje para variables cualitativas, así como la media aritmética y la desviación estándar para variables cuantitativas. Todos los integrantes del grupo de estudio se curaron y disminuyó el gasto de material, pero el costo-efectividad fue mayor por ser menor el tiempo de curación. El té de Vimang® resultó eficaz para eliminar las manifestaciones clínicas de esa lesión y no hubo reacciones adversas, de manera que se logró la curación de los afectados con ahorro de tiempo y recursos.

Trastornos temporomandibulares en pacientes con maloclusiones

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Luis Soto Cantero

Full Text Available Introducción: existe una prevalencia de trastornos oclusales en gran medida relacionados con la presencia de disfunción temporomandibular. Objetivo: determinar el grado de disfunción temporomandibular según el Índice de Maglione en correspondencia con la prevalencia de maloclusiones en el área de salud del policlínico "Turcios Lima". Métodos: se realizó un estudio observacional descriptivo, de corte transversal, en la consulta de ortodoncia, de junio del 2008 a junio del 2009. De un universo constituido por los 280 pacientes que acudieron al servicio de ortodoncia en el período señalado con presencia de maloclusiones, se seleccionó una muestra de 84 pacientes por muestreo aleatorio simple, teniendo en cuenta los criterios de inclusión y exclusión realizados por criterios de expertos. Resultados: presentaban disfunción temporomandibular 74 pacientes y dentro de ellos 44 (52,4 % tenían disfunción grado II (Moderada. El 97 % de los pacientes con relación molar de clase II, presentaban disfunción temporomandibular. El 42,9 % de los pacientes con una maloclusión, presentaban disfunción grado I. El 60 % de los pacientes con dos maloclusiones presentaban disfunción grado II y el 66,7 % de los pacientes con tres maloclusiones, presentaban disfunción grado III. La mayor cantidad de pacientes tuvieron disfunción grado II (Moderada. Conclusiones: el mayor por ciento de los pacientes con disfunciones presentó una clase II molar y a medida que aumentó el número de maloclusiones aumentó también la severidad de la disfunción.

Hepatitis B infection reported with cancer chemotherapy: analyzing the US FDA Adverse Event Reporting System.

Science.gov (United States)

Sanagawa, Akimasa; Hotta, Yuji; Kataoka, Tomoya; Maeda, Yasuhiro; Kondo, Masahiro; Kawade, Yoshihiro; Ogawa, Yoshihiro; Nishikawa, Ryohei; Tohkin, Masahiro; Kimura, Kazunori

2018-04-16

We conducted data mining using the US Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) database on spontaneously reported adverse events to evaluate the association between anticancer drug therapy and hepatitis B infection. Reports of hepatitis B infection were retrieved from the FAERS database. The reporting odds ratio (ROR) was used to estimate the association between hepatitis B infection and various anticancer agents and drug combinations. We detected statistically significant risk signals of hepatitis B for 33 of 64 anticancer agents by ROR (26 cytotoxicity drugs and seven molecular-targeted drugs). We focused on molecular-targeted drugs and assessed the risk of hepatitis B from specific anticancer drug combinations. The frequency of hepatitis B infection was significantly high for drugs such as rituximab, bortezomib, imatinib, and everolimus. The addition of cyclophosphamide, doxorubicin, and fludarabine to drug combinations additively enhanced the frequency of hepatitis B infection. There were no reports on hepatitis B infection associated with trastuzumab or azacitidine monotherapy. However, trastuzumab-containing regimens (e.g., combinations with docetaxel or paclitaxel) were correlated with the incidence of hepatitis B infection, similar to azacitidine monotherapy. Our findings suggest that the concomitant use of anticancer drugs, such as trastuzumab, taxane, and azacitidine, may contribute to the risk of hepatitis B infection. The unique signals detected from the public database might provide clues to eliminate the threat of HBV in oncology. © 2018 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Paraneoplastic Seronegative Pauci-Immune Glomerulonephritis Associated with Lung Adenocarcinoma Responds to Rituximab: A Case Report

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Pragnan Kancharla

2018-06-01

Full Text Available Anti-neutrophil cytoplasmic antibodies (ANCA play an important role in the pathogenesis of pauci-immune renal vasculitis. However, in 10% of the cases, ANCA are absent. We present a case of a 64-year-old man with a chronic untreated hepatitis C virus infection and Middle Eastern thalassemia who was ANCA-negative when he was hospitalized due to acute kidney injury and accounts for an uncommon presentation of renal vasculitis. The patient had earlier reported to have undergone local lobectomy and adjuvant chemotherapy (carboplatin/pemetrexed for lung adenocarcinoma a month prior. IL-6 has been reported to be involved in the pathophysiological cascade causing pauci-immune glomerulonephritis amongst non-small cell lung cancer patients. Previous studies with subgroup analysis have demonstrated that ANCA negativity has been associated with more chronic glomerular lesions and less crescent formation, which tends to have a critical outcome in the renal system. However, our patient underwent kidney biopsy exhibiting active crescentic glomerulonephritis, pauci-immune type with 5 cellular crescents amongst 15 glomeruli. To our knowledge, this is the third reported case of ANCA-negative vasculitis with typical presentation on biopsy in non-small cell lung cancer patients.

Revisión anatomofuncional de la neurología visual. Reporte de caso: discapacidad visual neurológica pos-TEC con hematomas subdurales subcrónicos bilaterales parietooccipitales

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Esteban O. Vallejo Agudelo

2016-01-01

Full Text Available El TEC según la IBIA es la principal causa de convulsiones, muerte y discapacidad adquirida mundialmente. Las principales causas son las caídas en mayores de 65 años y los accidentes de tránsito en los menores. Los hematomas pos-TEC son una complicación muy frecuente, cuyas manifestaciones son variables, especialmente en los subdurales, presentando desde cefalea hasta síndromes demenciales o déficit neurológico focal, dentro de los cuales no es usual el reporte de casos con manifestaciones visuales. El presente artículo reporta un caso de discapacidad visual por déficit neurológico pos-TEC complicado con hematomas subdurales subcrónicos bilaterales parietooccipitales, y revisa la neuroanatomía funcional visual involucrada en ella.

Tratamiento ortodóntico en paciente con periodontits crónica avanzada generalizada: reporte de un caso

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Iván Enrique Porto Cortés

2016-01-01

Full Text Available El tratamiento de ortodoncia es un procedimiento que busca corregir la maloclusión y mejorar la estética dental a través de fuerzas leves por periodos de tiempos largos o medianos, dicho tratamiento en pacientes periodontalmente comprometidos genera polémica debido a que la colocación de la aparatología puede incrementar la formacion de biopelicula y por ende agravar la periodontitis; también las fuerzas ejercidas podrían aumentar la reabsorción ósea. Sin embargo, en la actualidad se pueden encontrar estudios que confirman que el tratamiento de ortodoncia ayuda al periodonto enfermo gracias a los diferentes movimientos dentales que se producen durante éste; siempre y cuando el ortodoncista y periodoncista trabajen en conjunto, eduquen y motiven al paciente a cambiar sus hábitos de higiene bucal y sigan unos parámetros determinados. El objetivo principal del artículo es la presentación de un caso clínico en el que se realizó un tratamiento de ortodoncia a un paciente con periodontitis crónica avanzada generalizada y con relación canina clase III para de detener el avance de esta enfermedad, además para corregir la maloclusión y lograr una buena estética facial y dental. En conjunto con este tratamiento se realizaron procedimientos de mantenimiento periodontal tales como profilaxis dental, fase higiénica y enseñanza en higiene bucal. Los resultados del tratamiento se consideraron satisfactorios, se culminó sin pérdida dentaria, con oclusión en clase 1 de Angle, una buena estética facial y dental, un periodonto sano y un paciente educado en higiene bucal.

RadCon: A Radiological Consequences Model

International Nuclear Information System (INIS)

Crawford, J.; Domel, R.U.

2000-05-01

RadCon estimates the dose received by user selected groups in the population from an accidental release of radionuclides to the environment. The exposure pathways considered are external exposure from the cloud and ground and internal exposure from inhalation and ingestion of contaminated food. Atmospheric dispersion modelling is carried out externally to RadCon.Given a two dimensional time varying air and ground concentration of radioactive elements, RadCon allows the user to: view the air and ground concentration over the affected area, select optional parameters and calculate the dose to people,display the results to the user, and change the parameter values. RadCon offers two user interfaces: 1) the standard graphical user interface which is started using Java DoseApp at the command line, or by setting up a shortcut to this command (particularly when RadCon is installed on a PC) and 2) the text based interface used to generate information for the model inter-comparison exercise . This is initiated using Java BIOMASS at the command line, or an equivalent shortcut. The text based interface was developed for research purposes and is not generally available. Appendices A, B and C provide a summary of instructions on setting up RadCon. This will generally be carried out by the computer support personnel

Mesenchymal Stem Cells May Ameliorate Nephrotic Syndrome Post-Allogeneic Hematopoietic Stem Cell Transplantation-Case Report

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Xin Zhang

2017-08-01

Full Text Available IntroductionBecause of their immunomodulatory and anti-inflammatory effects, mesenchymal stem cells (MSCs have been considered as potential therapeutic agents for treating immune-related or autoimmune diseases, such as graft-versus-host disease (GVHD. Nephrotic syndrome (NS after allogeneic hematopoietic stem cell transplantation (allo-HSCT is an uncommon complication with unclear etiology and pathogenesis. It may be an immune disorder involving immune complex deposition, B cells, regulatory T cells (Tregs, and Th1 cytokines and be a manifestation of chronic GVHD. Corticosteroids and calcium antagonists, alone or in combination, are the most common therapeutic agents in this setting. Rituximab is commonly administered as salvage treatment. However, treatment failure and progressive renal function deterioration has been reported to occur in approximately 20% of patients in a particular cohort.Case presentationWe present a patient who developed NS 10 months after allo-HSCT. After treatment failure with cyclosporine A, prednisone, and rituximab, she achieved a complete response with MSC treatment. The clinical improvement of this patient was accompanied by a decreased B cell population together with an increased frequency of regulatory B cells (Bregs and Tregs after MSC treatment.ConclusionMSCs could modulate NS after allo-HSCT by suppressing B cell proliferation, inducing Tregs and Bregs, and inhibiting inflammatory cytokine production by monocytes and NK cells. Among all these, Bregs might play an important role in ameliorating the NS of this patient.

EuroQol-5 dimensions utility gain according to British and Swedish preference sets in rheumatoid arthritis treated with abatacept, rituximab, tocilizumab, or tumour necrosis factor inhibitors

DEFF Research Database (Denmark)

Gülfe, Anders; Wallman, Johan K; Kristensen, Lars Erik

2016-01-01

were plotted over time. RESULTS: Data regarding 2418 treatment courses with abatacept (ABA, n = 100), rituximab (RTX, n = 230), tocilizumab (TOC, n = 121), or TNFi (n = 1967) were included in the analysis. Patients starting TNFi treatment, as expected, had shorter disease duration and less previous...... biologics. Baseline utilities of patients commencing ABA and TOC, but not RTX, were also lower than in the TNFi group. Following treatment initiation, rapid utility improvements were seen with all therapies, reaching plateaus after approximately 1.5 months, and then remaining fairly stable throughout follow......-up in patients adhering to therapy. SE utilities were consistently higher than UK, with baseline values at around 0.7 leaving little room for improvement. CONCLUSIONS: ABA, RTX, TOC, and TNFi treatments were all associated with favourable EQ-5D utility developments in RA patients adhering to therapy...

Manifestaciones mucocutaneas en pacientes con lupus eritematoso sistemico

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V. Saurit

2003-08-01

Full Text Available El objetivo fue estudiar en pacientes con lupus eritematoso sistémico (LES la prevalencia de las lesiones mucocutáneas. Se incluyeron 77 pacientes. Las lesiones mucocutáneas fueron clasificadas en específicas y no específicas. Se definió el fototipo, exposición solar y fotoprotección. Se relacionaron las lesiones con la serología y la actividad de la enfermedad. Las lesiones específicas encontradas fueron: agudas (67.5%, lupus subagudo (6.3% y lesiones crónicas (26.0%. Las lesiones no específicas fueron: alopecia difusa (59%, fotosensibilidad (57%, fenómeno de Raynaud (47%, úlceras orales (16% y livedo reticularis (12%. El fototipo 3 (35% fue predominante; la exposición a las radiaciones ultravioletas fue moderada en 74%. Sólo 47% utilizaron protectores solares. Los anticuerpos anti-Ro se relacionaron en forma significativa con eritema malar, fotosensibilidad, livedo reticularis y alopecia. Los anticuerpos anti-Sm se relacionaron con fenómeno de Raynaud. Todas estas lesiones se observaron con mayor frecuencia en pacientes con enfermedad activa. La prevalencia de las manifestaciones mucocutáneas fue ligeramente más elevada a la informada en otras series. Hubo mayor prevalencia de eritema malar, alopecia difusa, fotosensibilidad y livedo reticularis en pacientes con enfermedad activa y anti-Ro (+ y de fenómeno Raynaud con anti-Sm.(+.The objective was to analyze the prevalence of mucocutaneous lesions in patients with systemic lupus erythematosus (SLE. During a 3-year period, we analyzed 77 patients with a diagnosis of SLE. The mucocutaneous lesions were classified into specific and non-specific. We defined skin type, sunlight exposure and photoprotection and correlated these lesions with serology and disease activity. Acute specific lesions were found in 67.5% of the patients, subacute lupus in 6.5% and chronic lesions in 26.0%. The most prevalent non-specific lesions were alopecia (59.7%, photosensitivity (57.1%, Raynaud

Influence of protic ionic liquids on the structure and stability of succinylated Con A.

Science.gov (United States)

Attri, Pankaj; Venkatesu, Pannuru

2012-01-01

We report the synthesis of a series of ionic liquids (ILs) from various ions having different kosmotropicity including dihydrogen phosphate (H(2)PO(4)(-)), hydrogen sulfate (HSO(4)(-)) and acetate (CH(3)COO(-)) as anions and chaotropic cation such as trialkylammonium cation. To characterize the biomolecular interactions of ILs with protein, we have explored the stability of succinylated Con A (S Con A) in the presence of these aqueous ILs, which are varied combinations of kosmotropic anion with chaotropic cation such as triethylammonium dihydrogen phosphate [(CH(3)CH(2))(3)NH][H(2)PO(4)] (TEAP), trimethylammonium acetate [(CH(3))(3)NH][CH(3)COO] (TMAA), trimethylammonium dihydrogen phosphate [(CH(3))(3)NH][H(2)PO(4)] (TMAP) and trimethylammonium hydrogen sulfate [(CH(3))(3)NH][HSO(4)] (TMAS). Circular dichroism (CD) and fluorescence experiments have been used to characterize the stability of S Con A by ILs. Our data distinctly demonstrate that the long alkyl chain IL TEAP is a strong stabilizer for S Con A. Further, our experimental results reveal that TEAP is an effective refolding enhancer for S Con A from a thermally denatured protein structure. Copyright © 2012 Elsevier B.V. All rights reserved.

Relevance of the immunoglobulin VH somatic mutation status in patients with chronic lymphocytic leukemia treated with fludarabine, cyclophosphamide, and rituximab (FCR) or related chemoimmunotherapy regimens.

Science.gov (United States)

Lin, Katherine I; Tam, Constantine S; Keating, Michael J; Wierda, William G; O'Brien, Susan; Lerner, Susan; Coombes, Kevin R; Schlette, Ellen; Ferrajoli, Alessandra; Barron, Lynn L; Kipps, Thomas J; Rassenti, Laura; Faderl, Stefan; Kantarjian, Hagop; Abruzzo, Lynne V

2009-04-02

Although immunoglobulin V(H) mutation status (IgV(H) MS) is prognostic in patients with chronic lymphocytic leukemia (CLL) who are treated with alkylating agents or single-agent fludarabine, its significance in the era of chemoimmunotherapy is not known. We determined the IgV(H) somatic mutation status (MS) in 177 patients enrolled in a phase 2 study of fludarabine, cyclophosphamide, and rituximab (FCR) and in 127 patients treated with subsequent chemoimmunotherapy protocols. IgV(H) MS did not impact significantly on the complete remission (CR) rate of patients receiving FCR or related regimens. However, CR duration was significantly shorter in patients with CLL that used unmutated IgV(H) than those whose CLL used mutated IgV(H) (TTP 47% vs 82% at 6 years, P IgV(H) MS emerged as the only determinant of remission duration (hazard ratio 3.8, P IgV(H) status.

Reporte de un caso de coexistencia de feocromocitoma y adenoma cortical adrenal en un paciente con hipertensión severa Report of a case of coexistence of pheochromocytoma and adrenal cortical adenoma in a patient with severe hypertension

Directory of Open Access Journals (Sweden)

César A Restrepo

2012-06-01

Full Text Available Se reporta el caso de una paciente con hipertensión paroxística asociada a síntomas adrenérgicos, en quien se encontraron niveles elevados de metanefrinas totales en orina de 24 horas, hipopotasemia persistente y nódulo en la glándula suprarrenal. Fue llevada a cirugía en la que se identificaron dos masas suprarrenales, una con características histológicas de feocromocitoma y otra de adenoma suprarrenal.We report the case of a female patient with paroxysmal hypertension associated with adrenergic symptoms. Elevated levels of total metanephrines in 24 hour urine were found, as well as persistent hypokalemia and a nodule in the adrenal gland. She was taken to surgery, and two adrenal masses were identified, one with histological characteristics of pheochromocytoma and another one of adrenal adenoma.

A first-in-man phase 1 trial for long-acting TransCon Growth Hormone.

Science.gov (United States)

Gilfoyle, David; Mortensen, Eva; Christoffersen, Eva Dam; Leff, Jonathan A; Beckert, Michael

2018-04-01

TransCon growth hormone (GH) is a sustained-release inactive prodrug consisting of unmodified GH transiently bound to an inert carrier molecule designed to release fully active GH over a one-week period. This was a first-in-man phase 1 randomized trial was to evaluate the safety, tolerability, immunogenicity, pharmacokinetics (PK), and pharmacodynamics (PD) of a single dose of TransCon GH as compared to equivalent doses of daily GH (Omnitrope) or placebo in healthy adults. Forty-four healthy male adults were randomized to 4 cohorts of 11 subjects, distributed in a 7:2:2 ratio (TransCon GH: Omnitrope: placebo). A single injection of 4 possible TransCon GH doses (i.e., 0.04, 0.08, 0.16, or 0.24mg GH/kg/wk) or two different Omnitrope doses (i.e., 0.08 or 0.16mg GH/kg/wk divided into 7 equal daily doses) were administered with subjects evaluated for adverse events, immunogenicity, and GH and insulin-like growth factor-1 (IGF-1) levels. TransCon GH was well tolerated; no serious adverse events occurred, no injection site reaction differences between TransCon GH, Omnitrope, or placebo were identified, no nodules or lipoatrophy were reported, and no anti-GH binding antibodies or ECG changes were detected. Overall, the exposure of GH (C max ) and IGF-1 (AUC 0-168h ) following administration of equivalent doses of TransCon GH and Omnitrope were similar. GH and IGF-1 kinetics showed a dose-proportional increase following a single SC administration of TransCon GH and indicated that the prodrug is suitable for weekly administration. These results support advancement of TransCon GH to pediatric and adult GHD trials. Clinical trial registration numbers: NCT01010425 (clinicaltrials.gov). Copyright © 2017 Elsevier Ltd. All rights reserved.

Estudio comparativo del efecto del cepillado con una crema dental con propóleos rojos y de un gel con clorofila

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Estela Gispert Abreu

1998-12-01

Full Text Available Se analiza comparativamente el efecto de un gel dental de clorofila y de una crema dental con propóleos rojos sobre varios parámetros relacionados con la caries dental, en escolares que se cepillaron durante 21 días con dichos productos. Se obtuvieron resultados favorables principalmente en la disminución del grado de infección por Streptococcus mutans y la elevación de la capacidad individual de remineralización; salvo en este último no hubo diferencias estadísticamente significativas.Authors made a comparative analysis about effect of chlorophyl dental gel and toothpaste containing red propolis, on some parameters related to dental caries in a group of students that brushed their teeth during 21 days using such products. Favourable results were obtained, mainly in decrease of infection level from Streptococcus mutans, and in increase of individual capacity of remineralization; except for this latter, there weren´t statistically significant differences.

Tratamiento conservador en pacientes con retinoblastoma bilateral

Directory of Open Access Journals (Sweden)

Juan C. Suárez

2008-11-01

Full Text Available OBJETIVO: comparar el tratamiento convencional del retinoblastoma bilateral, usado hasta hace algunos años, consistente en radioterapia o enucleación bilateral, con el tratamiento conservador actual que incluye termoterapia transpupilar (TTT o TTT/quimioterapia al menos en un ojo, en niños con diagnóstico de retinoblastoma bilateral. DISEÑO: estudio retrospectivo descriptivo. MUESTRA: 20 pacientes con diagnóstico de retinoblastoma bilateral que consultaron al Hospital Universitario San Vicente de Paúl, de Medellín, Colombia, entre 1997 y 2007. MÉTODO: se hizo enucleación del ojo con el tumor de mayor tamaño. En el otro ojo se hizo tratamiento con TTT, con el láser diodo (810 nm, spot amplio, solo o combinado con otras terapias. RESULTADOS: se dividió a los pacientes en dos grupos: 16 pacientes (32 ojos en el grupo 1 tratados conservadoramente y 4 pacientes (8 ojos en el grupo 2 con tratamiento convencional. El rango de edad fue de 1-72 meses en el grupo 1 y de 1-12 meses en el grupo 2. El tiempo de seguimiento fue de 7-67 meses para el grupo 1 y de 13-73 meses para el grupo 2. En el grupo 1 se hizo enucleación de 16 ojos (50%, radioterapia externa de uno (3,1%, quimioterapia más termoterapia de 5 (15,6% y quimioterapia más termoterapia más crioterapia de 10 (31,3%. En todos los pacientes se logró preservar al menos un ojo. En el grupo 2, se enuclearon 7 ojos (87,5% y se hizo radioterapia externa más enucleación en un paciente (12.5%. Además, todos los pacientes recibieron quimioterapia. CONCLUSIÓN: la terapia conservadora actual consistente en tratamiento local (termoterapia, crioterapia o braquiterapia y quimiorreducción permite preservar al menos un ojo y en algunos casos de los dos, muchas veces con buena agudeza visual, en niños con retinoblastoma bilateral; se evitan así la enucleación bilateral y la radioterapia externa usada en el tratamiento convencional con todos sus efectos secundarios. La enucleación contin

Variables socionutricionales de hogares mazahuas integrados por preescolares desnutridos con madres con obesidad y sin obesidad

OpenAIRE

Viridiana Vanessa Conzuelo-González

2009-01-01

El primer objetivo fue conocer cuántos menores de cinco años con diferentes grados de desnutrición tienen una madre con sobrepeso/obesidad/ en una comunidad indígena que vive en extrema pobreza y bajo condiciones de migración masculina internacional. El segundo fue comparar tres variables socionutricionales (ingreso familiar, educación de la madre y adecuación nutrimental de la dieta diaria) entre estos hogares y los hogares con desnutrición infantil y madres sin obesidad. Se realizó un estud...

Terapia asistida con perros en niños con autismo revisión sistemática

OpenAIRE

Isaza Narváez, Ana Milena; Muñoz Chilito, Doumer Adrian

2013-01-01

Introducción: El autismo es un trastorno temprano y masivo del desarrollo en el cual se afecta la interacción social, el desarrollo del lenguaje, se presentan rituales y estereotipias. Hay evidencia que la interacción con un perro está asociada con efectos positivos en la salud del niño, lo cual se extiende al terreno terapéutico donde la compañía del perro estimula habilidades comunicativas para conectarse con el mundo exterior y romper el aislamiento que lo hace refractario a formas convenc...

Variables socionutricionales de hogares mazahuas integrados por preescolares desnutridos con madres con obesidad y sin obesidad

OpenAIRE

Viridiana Vanessa Conzuelo-González; Ivonne Vizcarra-Bordi

2009-01-01

El primer objetivo fue conocer cuántos menores de cinco años con diferentes grados de desnutrición tienen una madre con sobrepeso/obesidad/ en una comunidad indígena que vive en extrema pobreza y bajo condiciones de migración masculina internacional. El segundo fue comparar tres variables socionutricionales (ingreso familiar, educación de la madre y adecuación nutrimental de la dieta diaria) entre estos hogares y los hogares con desnutrición infantil y madres sin obesidad. Se realizó un est...

Diabetes insipidus due to herpes encephalitis in a patient with diffuse large cell lymphoma. A case report.

Science.gov (United States)

Scheinpflug, K; Schalk, E; Reschke, K; Franke, A; Mohren, M

2006-01-01

The major causes of central diabetes insipidus are neoplastic or infiltrative lesions of the hypothalamus or pituitary, severe head injuries and pituitary or hypothalamic surgery. Central diabetes insipidus caused by viral infections has been rarely reported in immunosuppressed patients, such as those with acquired immunodeficiency syndrome or Cushing's syndrome. We report the case of a 48-year-old woman suffering from diffuse large cell lymphoma, who developed hypotonic polyuria, hypernatriaemia and somnolence after the first course of chemotherapy with CHOEP and rituximab. Diabetes insipidus was diagnosed by low urine osmolarity and an undetectable vasopressin concentration. MRI revealed no pituitary abnormalities but encephalitis, and lumbar punction confirmed herpes zoster infection. To the best of our knowledge this is the first description of central diabetes insipidus in a lymphoma patient caused by an opportunistic CNS-infection.

Efectos del contacto piel con piel del recién nacido con su madre

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Camila Lucchini Raies

Full Text Available Antecedentes: el contacto piel con piel ha sido una práctica ancestral en toda cultura, que debido a la institucionalización de la atención del parto, disminuyó en occidente. Se retomó en el marco de la atención humanizada del parto. Objetivo principal: determinar los efectos del contacto piel con piel del recién nacido con su madre. Metodología: revisión bibliográfica de 26 estudios. Límites de búsqueda: new borns, humans, clinical trials, de 10 años de publicación, en bases de datos: Pubmed, ProQuest, CINHAL, Lilacs. Resultados principales: Se observaron beneficios en las variables: duración de lactancia materna, comportamiento neurosensorial, regulación de temperatura, como alternativa al cuidado estándar, disminución en días hospitalización y niveles de cortisol, favorecedor de la interacción madre-hijo y desarrollo infantil. Conclusión principal: el contacto piel con piel brinda múltiples beneficios a recién nacidos. Se presenta como alternativa de cuidado segura, factible de implementar.

Macroglosia asociada con deformidades dentofaciales: Alternativas terapéuticas y presentación de un caso Macroglossia associated with dentofacial deformities: Therapeutic alternatives and a case report

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José Manuel Díaz Fernández

2006-12-01

Full Text Available Se lleva a efecto una revisión bibliográfica de las alternativas de tratamiento en la corrección de la macroglosia asociada con deformidades dentofaciales. Se establecen las alternativas quirúrgicas ortodóncicas, así como las indicaciones y ventajas de cada variante operatoria. Se presenta un caso clínico donde ambas condiciones patológicas están presentes. Se emiten algunas consideraciones cuando se ejecuta una glosectomía de reducción en pacientes con anomalías dentofaciales.A bibliographic review of the treatment alternatives for the correction of macroglossia associated with dentofacial deformities is made. The surgical orthodontic alternatives are established, as well as the indications and advantages of every operative variant. A clinical case with both pathological conditions is reported. Some considerations are given when a reduction glossectomy is performed in patients with dentofacial abnormalities.

Larvicultura de Rhamdia quelen (Pisces, Pimelodidae con proteína vegetal y animal, suplementadas con plancton

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Germán Castañeda A.

2011-12-01

Full Text Available Objetivo. Determinar el efecto de dietas con diferentes proporciones de fuentes proteicas animales y vegetales suplementadas con plancton sobre el crecimiento y sobrevivencia en larvas de Rhamdia quelen. Materiales y métodos. Fueron formuladas dos dietas experimentales, dieta-1 con 70% de proteína de origen vegetal (torta de soya y dieta-2 con 70% de proteína proveniente de animales (corazón bovino yharina de pescado; se utilizaron cuatro protocolos de alimentación (cinco réplicas por tratamiento: dieta-1 + plancton filtrado en tamiz de 50-200 micras (T1, dieta-2 + plancton filtrado en tamiz de 50-200 micras (T2, dieta-1 (T3, dieta-2 (T4. Las larvas fueron manejadas a una densidad de 20 animales L-1 suministrando alimentohasta aparente saciedad diariamente a las 07:00, 11:00, 16:00 y 21:00 horas; la suplementación con plancton se realizó a las 11:00 y 21:00 horas. Resultados. Entre T1 y T2 no se observaron diferencias estadísticas (p>0.05 en peso final (21.89 ± 15.17mg vs 20.37 ± 10.37mg, longitud total (13.41±2.34mm vs 13.39±1.99 mm, factor de condición (K (0.80±0.13 vs 0.78±0.13 y sobrevivencia (46.6±2.68% vs36.0±7.41%; las diferencias entre T3 y T4 tampoco fueron significativas (3.35±1.40 mg vs 2.98±1.48 mg; 7.54±0.91mm vs 7.33±0.96mm; 0.75±0.13 vs 0.71±0.12; 33.6±9.07% vs 24.8±6.76%, respectivamente; hubo diferencias significativas (p<0.05 entre los grupos suplementados con plancton y los alimentados solo con ración. Conclusiones. La suplementación con plancton fue más efectiva que elofrecimiento solo de ración. La inclusión del 62.9% de torta de soya en la formulación (T1, aparentemente no afectó el crecimiento ni la sobrevivencia.

Ensayo clínico con intervención educativa en mujeres perimenopáusicas con un factor de riesgo cardiovascular

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Anxela Soto-Rodríguez

2017-01-01

Conclusiones: Una sencilla intervención educativa en mujeres perimenopáusicas con un factor de riesgo cardiovascular mejora aspectos relacionados con la calidad de vida y con hábitos saludables como la actividad física.

Soporte social con el uso de tic’s para cuidadores familiares de personas con enfermedad crónica

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Carrillo, Gloria Mabel; Chaparro, Olivia Lorena; Barrera, Lucy; Sanchez, beatriz; Pinto, Raquel Natividad

2012-01-01

Objetivo Determinar la efectividad del soporte social dado con el uso de tecnologías de la información y la comunicación (TIC’S) a los cuidadores familiares de personas con enfermedad crónica.  Material y Métodos. Estudio descriptivo, exploratorio realizado en Bogotá en 2008 y 2009 con 144 cuidadores familiares de personas con enfermedad crónica  que constó de tres etapas para su desarrollo: 1. Planeación, diseño de la TIC’s,  aplicación de  prueba piloto y  selección de  población objeto;  ...

CHANGES OF BONE MINERAL DENSITY DURING FOUR-YEAR RITUXIMAB AND METHOTREXATE THERAPY IN POSTMENOPAUSAL WOMEN WITH RHEUMATOID ARTHRITIS

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T. A. Raskina

2016-01-01

Full Text Available Objective: to estimate the changes of bone mineral density (BMD  at the femoral neck and lumbar spine during fouryear combination  therapy with rituximab (RTM  and methotrexate (MT in postmenopausal women with rheumatoid arthritis (RA.Subjects and methods. 79 postmenopausal women with a documented diagnosis of RA were followed up. They were divided into two groups according to the basic treatment:  1 44 patients received combination  therapy with RTM and MT; 2 36 patients had MT monotherapy. BMD was assessed by dual-energy X-ray absorptiometry using an Excell XR-46 stationary dual-energy X-ray bone densitometer  (Norland, USA once per year (over 48 months.Results and discussion. The group of patients receiving RTM and MT achieved a statistically significant increase in femoral neck BMD after 36 months of therapy. Statistically significant changes in femoral neck BMD were not revealed in the patients who had MT monotherapy. Lumbar spine BMD was decreased during MT monotherapy, but it remained stable in the RTM + MT group throughout  the 48-month follow-up.Conclusion. Thirty-six-month combination  treatment with RTM and MT provides positive changes in femoral neck BMD, which persists within 48 months after treatment initiation.  Lumbar spine BMD remained stable in the patients receiving RTM and MT.

Adolescente femenino con granulomatosis de Wegener fulminante

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S C Scheffler-Mendoza

2017-01-01

Full Text Available Adolescente femenino de 13 años de edad, originaria de Guerrero, grupo étnico mixteco, padres analfabetos y con poco entendimiento del español. Sin otros antecedentes de importancia para el padecimiento. Inició un mes previo con la aparición de una pápula hipercrómica en párpado superior derecho que en los 10 días previos al ingreso aumentó de volumen generando proptosis. Al interrogatorio se negó dolor, lagrimeo, fiebre, o pérdida de peso. Ingresó con fiebre (39.0°C, palidez generalizada, proptosis derecha con exposición de córnea y conjuntiva, eritema periorbitario, movimientos oculares y agudeza visual disminuidos (i.e. contaba dedos a 1 m, pupila con tendencia a midriasis, hiperreactividad a la luz, y fondo de ojo con papila hiperémica edematosa y tortuosidad peripapilar. El resto de exploración no mostró datos relevantes. Se hospitalizó para iniciar tratamiento antimicrobiano parenteral de amplio espectro (i.e. ceftriaxona y vancomicina y abordar proptosis unilateral.

INSUFICIENCIA RENAL AGUDA CON UREMIA NORMAL EN PACIENTE MONO-RENO SECUNDARIA A PIELONEFRITIS AGUDA

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Musso CG

2006-03-01

Full Text Available RESUMEN:La insuficiencia renal aguda es un sindrome que característicamente cursa con niveles plasmáticos elevados de urea y creatinina. Sin embargo, hay situaciones clínicas en las cuales este sindrome puede cursar con un incremento de la creatininemia sin presentar elevación de la uremia.En este reporte presentamos un caso clínico de una insuficiencia renal aguda con uremia normal secundaria a una pielonefritis aguda en un paciente con riñón único. El paciente presentaba una elevada excreción fraccional de urea lo cual podía explicar su uremia normal pese a estar cursando una caída del filtrado gomerular. Dicha excreción de urea elevada fue interpretada como secundaria a una diabetes insipida nefrogénica y una alteración en el recirculado intra-renal de la urea ambos producto de la pielonefritis aguda. Concluimos que la pielonefritis aguda en un paciente mono-reno puede presentarse con un patrón de insuficiencia renal aguda con uremia normal. SUMMARYAcute renal failure is a syndrome that usually runs with an increase in creatinine and urea plasma levels. However, there are clinical situations in which this syndrome may run with an increase in plasma creatinine keeping normal the urea one.In this report we present a case of acute renal failure with normal plasma urea level secondary to an acute pyelonephritis in a single kidney patient. The patient had an increased fractional excretion of urea which could explain the normal plasma urea levels found despite of his reduced glomerular filtration. This increased urea excretion state was interpreted as a consequence of the nephrogenic diabetes insipidus and alteration of the intra-renal urea reciclying process that the acute pyelonephritis induced. In conclusion: Acute pyelonephritis in a single kidney patient can appear as a pattern of acute renal failure with normal plasma urea levels.

INSUFICIENCIA RENAL AGUDA CON UREMIA NORMAL EN PACIENTE MONO-RENO SECUNDARIA A PIELONEFRITIS AGUDA

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Musso CG

2007-04-01

Full Text Available RESUMENLa insuficiencia renal aguda es un sindrome que característicamente cursa con niveles plasmáticos elevados de urea y creatinina. Sin embargo, hay situaciones clínicas en las cuales este sindrome puede cursar con un incremento de la creatininemia sin presentar elevación de la uremia. En este reporte presentamos un caso clínico de una insuficiencia renal aguda con uremia normal secundaria a una pielonefritis aguda en un paciente con riñón único. El paciente presentaba una elevada excreción fraccional de urea lo cual podía explicar su uremia normal pese a estar cursando una caída del filtrado gomerular. Dicha excreción de urea elevada fue interpretada como secundaria a una diabetes insipida nefrogénica y una alteración en el recirculado intra-renal de la urea ambos producto de la pielonefritis aguda. Concluimos que la pielonefritis aguda en un paciente mono-reno puede presentarse con un patrón de insuficiencia renal aguda con uremia normal.SUMMARYAcute renal failure is a syndrome that usually runs with an increase in creatinine and urea plasma levels. However, there are clinical situations in which this syndrome may run with an increase in plasma creatinine keeping normal the urea one. In this report we present a case of acute renal failure with normal plasma urea level secondary to an acute pyelonephritis in a single kidney patient. The patient had an increased fractional excretion of urea which could explain the normal plasma urea levels found despite of his reduced glomerular filtration. This increased urea excretion state was interpreted as a consequence of the nephrogenic diabetes insipidus and alteration of the intra-renal urea reciclying process that the acute pyelonephritis induced. In conclusion: Acute pyelonephritis in a single kidney patient can appear as a pattern of acute renal failure with normal plasma urea levels.

Síntomas depresivos en pacientes con Trastorno por déficit de atención con hiperactividad.

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Diego Artemio Reátegui Villegas

2008-07-01

Full Text Available Objetivos: Determinar la frecuencia de síntomas depresivos en pacientes con Trastorno por déficit de atención con hiperactividad (TDAH, así como determinar su asociación con edad, sexo y comorbilidad psiquiátrica. Material y Método: Se realizó un estudio descriptivo de corte transversal. Se incluyeron pacientes con diagnóstico de TDAH del Instituto Nacional de Salud Mental Honorio Delgado Hideyo Noguchi, desde febrero del 2006 hasta completar el tamaño de la muestra. Se les aplicó a los pacientes el Children´s depression inventory (CDI. Se consideró un punto de corte de 15 para definir presencia de trastorno depresivo. Se analizaron las siguientes variables: edad, sexo, comorbilidad psiquiátrica y sintomatología depresiva. Resultados: Sesenta y cuatro (85,3% fueron varones, en 35/75 (46,7% se encontró CDI ³ 15. No se encontró asociación estadísticamente significativa entre síntomas depresivos y sexo o edad. El síntoma depresivo más frecuente fue el problema del rendimiento escolar (65,3%. Se encontraron 6 pacientes con otra comorbilidad. Conclusión: Existe una alta frecuencia de sintomatología depresiva en niños y adolescentes con diagnóstico de TDAH. (Rev Med Hered 2008;19:96-101 .

Linfoma de Burkitt primario de la cavidad oral en una paciente con sida. Reporte de un caso y revisión de la literatura

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Marcelo Corti

2015-01-01

Full Text Available Los linfomas no Hodgkin (LNH son un grupo heterogéneo de enfermedades linfoproliferativas con elevada prevalencia en pacientes infectados por el virus de la inmunodeficiencia humana (VIH. La inmunodeficiencia asociada al sida predispone al desarrollo de LNH, incluyendo el linfoma de Burkitt (LB. El LB es un subtipo infrecuente y agresivo de LNH con elevada frecuencia en pacientes con sida. Se asocia a una alta tasa de replicación celular (determinada por el índice Ki67 y con alta frecuencia de compromiso extranodal como forma de presentación clínica de la neoplasia. Se presenta una paciente con sida que desarrolló un LB primario de la cavidad oral y se realiza una revisión de la literatura sobre el tema.

disegnare con ... Alberto Pratelli

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Roberto Mingucci

2017-12-01

Full Text Available Con questa breve intervista ad Alberto Pratelli, (non a caso scelto per aprire questa nuova rubrica intendia-mo inaugurare un dialogo con personalità significati-ve del Disegno di Architettura, che consenta riflessioni dedicate alle sue varie dimensioni, oggi più che mai da approfondire. La suggestione a farlo, viene da un’idea di Pablo Rodri-guez Navarro ed abbiamo quindi pensato di avviarla proprio in questo numero, che Pablo ha accettato di curare su un tema a lui particolarmente caro.

Depresion en pacientes con alteraciones del tiroides

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Radanovic-Grguric´, Ljiljana; Filakovic´, Pavo; Barkic´, Jelena; Mandic´, Nikola; Karner, Ivan; Smoje, Juraj

2003-01-01

Nuestro estudio fue realizado en un grupo de 53 mujeres con disfunción tiroidea y 28 mujeres con depresión mayor. Empleamos la Escala de la Depresión de Hamilton, la Escala de Autoevaluación de la Depresión de Zung y la Escala sobre la Impresión Clínica Global. Los resultados del estudio demuestran que la mayoría de los pacientes con disfunción tiroidea se mostraron clínicamente significativos en cuanto al trastorno depresivo. Los episodios depresivos son más frecuentes en pacientes con hipot...

[Small vessel-childhood primary angiitis of the central nervous system: a case report and literature review].

Science.gov (United States)

Deng, J; Fang, F; Wang, X H; Ge, M; He, L J; Zhang, N

2018-02-02

Objective: To summarize the clinical and pathological features of small vessel-childhood primary angiitis of the central nervous system (SV-cPACNS), discuss the immune therapy and increase the attention to brain biopsy in SV-cPACNS. Methods: The clinical data, pathology of brain biopsy, treatment and outcome of an SV-cPACNS patient hospitalized in Beijing Children's Hospital in February 2016 were analyzed retrospectively. The cases reported at Pubmed, CNKI and Wanfang databases from 2007 to 2017 were searched, the clinical and pathological features, immunotherapy and prognosis of the disease were summarized according to the literature review. Results: A 70 months old girl had 6 times relapses during 5 months' disease course. Symptoms included convulsions, limb paralysis, blurred vision and speech difficulty. Multiple cortical lesions were found successively in brain MRI but CT angiography was negative. The pathology of brain biopsy revealed thickening of small vessel walls together with lymphocytic infiltration. After the treatment with rituximab, remission was achieved and remained stable without recurrence in 1 year follow up. A total of 44 pathologically confirmed cases reported in nearly 10 years were retrieved. Male to female ratio was 1∶3.5. The average onset age was 9.8 years. Clinical manifestations included seizures (37/45, 82%), headache (35/45, 78%), cognitive decline (28/45, 62%), speech regression(20/45, 44%), paralysis (15/45, 33%), and so on; 70% (19/27) patients experienced relapses. Erythrocyte sedimentation rate and C-reactive protein slightly elevated, antinuclear antibody and other autoimmune antibodies were mostly negative. Mild lymphocytosis in cerebrospinal fluid was found in 67%(29/43) patients. 53%(23/43) patients had elevated CSF protein level, several had elevated IgG and positive oligoclonal band. Bilateral multifocal lesions were revealed in 80% (36/45) brain MRIs, meanwhile all angiographies were unremarkable. The pathology showed

Enfermedad coronaria en pacientes con psoriasis

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Walter Masson

2013-10-01

Full Text Available Comunicaciones previas asociaron la psoriasis con la enfermedad coronaria. Desconocemos si en nuestro país o región existe dicha asociación. Se realizó un estudio transversal analizando los datos de la historia clínica electrónica de un sistema de salud de Buenos Aires. Analizamos todos los pacientes mayores de 18 años con diagnóstico de psoriasis entre el 1 de enero de 2003 y el 31 de julio de 2011 y los comparamos con un grupo control, en una relación 2:1, obtenido en forma aleatoria del mismo sistema de salud, apareados por edad y sexo. Determinamos la prevalencia de los factores de riesgo cardiovascular y de enfermedad coronaria. Analizamos la asociación entre la enfermedad coronaria y la psoriasis mediante análisis uni y multivariado. Se incluyeron 3 833 sujetos (1 286 pacientes con psoriasis y 2 547 controles. La prevalencia de hipertensión arterial (50% vs. 38%, p < 0.001, tabaquismo (25% vs. 17%, p < 0.001, diabetes (12% vs. 8%, p < 0.001 y enfermedad coronaria (4.98% vs. 3.06%, p = 0.003 fue mayor en los sujetos con psoriasis en comparación con el grupo control. Independientemente de la edad, la presencia de diabetes, hipertensión arterial o tabaquismo, hubo una asociación significativa entre la enfermedad coronaria y la psoriasis (OR 1.48, IC95% 1.04-2.11, p = 0.03. En conclusión, en esta población de Buenos Aires, los pacientes con psoriasis tuvieron una mayor prevalencia de diabetes, hipertensión arterial, tabaquismo y enfermedad coronaria. La asociación entre la psoriasis y la enfermedad coronaria fue independiente de los factores de riesgo explorados.

Mincle Signaling Promotes Con-A Hepatitis

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Greco, Stephanie H.; Torres-Hernandez, Alejandro; Kalabin, Aleksandr; Whiteman, Clint; Rokosh, Rae; Ravirala, Sushma; Ochi, Atsuo; Gutierrez, Johana; Salyana, Muhammad Atif; Mani, Vishnu R.; Nagaraj, Savitha V.; Deutsch, Michael; Seifert, Lena; Daley, Donnele; Barilla, Rocky; Hundeyin, Mautin; Nikifrov, Yuriy; Tejada, Karla; Gelb, Bruce E.; Katz, Steven C.; Miller, George

2016-01-01

Concanavalin-A (Con-A) hepatitis is regarded as a T cell-mediated model of acute liver injury. Mincle is a C-type lectin receptor (CLR) that is critical in the immune response to mycobacteria and fungi, but does not have a well-defined role in pre-clinical models of non-pathogen mediated inflammation. Since Mincle can ligate the cell death ligand SAP130, we postulated that Mincle signaling drives intrahepatic inflammation and liver injury in Con-A hepatitis. Acute liver injury was assessed in the murine Con-A hepatitis model using C57BL/6, Mincle−/−, and Dectin-1−/− mice. The role of C/EBPβ and HIF-1α signaling was assessed using selective inhibitors. We found that Mincle was highly expressed in hepatic innate inflammatory cells and endothelial cells in both mice and humans. Furthermore, sterile Mincle ligands and Mincle signaling intermediates were increased in the murine liver in Con-A hepatitis. Most significantly, Mincle deletion or blockade protected against Con-A hepatitis whereas Mincle ligation exacerbated disease. Bone marrow chimeric and adoptive transfer experiments suggested that Mincle signaling in infiltrating myeloid cells dictates disease phenotype. Conversely, signaling via other CLRs did not alter disease course. Mechanistically, we found that Mincle blockade decreased the NF-κβ related signaling intermediates, C/EBPβ and HIF-1α, both of which are necessary in macrophage-mediated inflammatory responses. Accordingly, Mincle deletion lowered production of nitrites in Con-A hepatitis and inhibition of both C/EBPβ and HIF1-α reduced the severity of liver disease. Our work implicates a novel innate immune driver of Con-A hepatitis and, more broadly, suggests a potential role for Mincle in diseases governed by sterile inflammation. PMID:27559045

Mincle Signaling Promotes Con A Hepatitis.

Science.gov (United States)

Greco, Stephanie H; Torres-Hernandez, Alejandro; Kalabin, Aleksandr; Whiteman, Clint; Rokosh, Rae; Ravirala, Sushma; Ochi, Atsuo; Gutierrez, Johana; Salyana, Muhammad Atif; Mani, Vishnu R; Nagaraj, Savitha V; Deutsch, Michael; Seifert, Lena; Daley, Donnele; Barilla, Rocky; Hundeyin, Mautin; Nikifrov, Yuriy; Tejada, Karla; Gelb, Bruce E; Katz, Steven C; Miller, George

2016-10-01

Con A hepatitis is regarded as a T cell-mediated model of acute liver injury. Mincle is a C-type lectin receptor that is critical in the immune response to mycobacteria and fungi but does not have a well-defined role in preclinical models of non-pathogen-mediated inflammation. Because Mincle can ligate the cell death ligand SAP130, we postulated that Mincle signaling drives intrahepatic inflammation and liver injury in Con A hepatitis. Acute liver injury was assessed in the murine Con A hepatitis model using C57BL/6, Mincle(-/-), and Dectin-1(-/-) mice. The role of C/EBPβ and hypoxia-inducible factor-1α (HIF-1α) signaling was assessed using selective inhibitors. We found that Mincle was highly expressed in hepatic innate inflammatory cells and endothelial cells in both mice and humans. Furthermore, sterile Mincle ligands and Mincle signaling intermediates were increased in the murine liver in Con A hepatitis. Most significantly, Mincle deletion or blockade protected against Con A hepatitis, whereas Mincle ligation exacerbated disease. Bone marrow chimeric and adoptive transfer experiments suggested that Mincle signaling in infiltrating myeloid cells dictates disease phenotype. Conversely, signaling via other C-type lectin receptors did not alter disease course. Mechanistically, we found that Mincle blockade decreased the NF-κβ-related signaling intermediates C/EBPβ and HIF-1α, both of which are necessary in macrophage-mediated inflammatory responses. Accordingly, Mincle deletion lowered production of nitrites in Con A hepatitis and inhibition of both C/EBPβ and HIF-1α reduced the severity of liver disease. Our work implicates a novel innate immune driver of Con A hepatitis and, more broadly, suggests a potential role for Mincle in diseases governed by sterile inflammation. Copyright © 2016 by The American Association of Immunologists, Inc.

Cementos con cenizas volantes

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Ossa M., Mauricio

1984-03-01

additions of 20 and 30% .

Casi la generalidad de los estudios realizados sobre cementos con adición de cenizas volantes se refieren a sus características y comportamiento en pastas, morteros y hormigones, siempre en relación con aquéllos del cemento portland. Esta vez, se desarrolló un trabajo experimental orientado a relacionar entre sí los cementos con adiciones de cenizas volantes y de puzolana natural. Para ello se fabricaron a escala de laboratorio cementos de ambos tipos, empleando como materias primas comunes clinker y yeso y, como variables, diferentes porcentajes de las dos adiciones, que cumplieron previamente los requisitos normalizados en cuanto a sus actividades puzolánicas. La calidad de los cementos fabricados resultó adecuada y concordante con la del cemento portland-puzolánico obtenido a escala industrial con los mismos clinker, yeso y puzolana natural de este estudio. Posteriormente, se determinaron las características de los cementos experimentales y se confeccionaron morteros normales para la realización de ensayos físicos y mecánicos. Los resultados de ensayos indicaron que los cementos con adición de cenizas volantes (CCV requieren menos agua para consistencia normal, presentan tiempos de fraguado mayores y expansiones en autoclave menores que los cementos con adición de puzolana (CP. Los calores de hidratación a 7 y 28 días de edad fueron aproximadamente similares para ambos tipos de cemento. En morteros normales, los cementos CCV mostraron menor retracción de secado, mayor retentividad y mayor fluidez (para igual cantidad de agua que los cementos CP. En los ensayos de exudación se observó que ésta depende más de la finura que el tipo de adición. Finalmente, los ensayos mecánicos señalaron que las resistencias a compresión y flexotracción de los morteros con cementos CCV son menores a edades inferiores que 14 días (del orden de 5 a 10% a un día de edad, pero que a partir de entonces pasan a ser mayores que las de

Cambios en el tono muscular en dos niños con parálisis cerebral espástica mediante la hipoterapia: reporte de casos

OpenAIRE

Rodríguez Laiseca, Yasmín Andrea; Lerma Castaño, Piedad Rocío

2015-01-01

Introducción: Estudios previos han demostrado que la hipoterapia como terapia complementaria mejora la función motora gruesa en niños con parálisis cerebral. Sin embargo la evidencia no es concluyente. Objetivo: Determinar los cambios en el tono muscular de dos pacientes con parálisis cerebral tipo cuadriparesia espástica mediante la hipoterapia. Descripción del caso: El estudio se llevó a cabo con dos sujetos de género masculino de dos años de edad, con diagnóstico de parálisis cerebral tipo...

Efecto de un tratamiento intensivo con insulina sobre la reactividad plaquetaria en pacientes con hiperglucemia que ingresan con un síndrome coronario agudo

OpenAIRE

Vivas Balcones, Luis David

2011-01-01

El objetivo primario de este trabajo ha sido la valoración del efecto que produce el control estricto de la glucemia mediante un tratamiento intensivo y precoz con insulina sobre la reactividad plaquetaria durante la fase hospitalaria en pacientes que ingresan en una unidad de cuidados intensivos cardiológicos con un síndrome coronario agudo e hiperglucemia, respecto a un tratamiento convencional.

Paniculitis en paciente con dermatomiositis Panniculitis in a patient with dermatomyositis

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Mariana Arias

2011-02-01

Full Text Available La paniculitis es una manifestación cutánea infrecuente de la dermatomiositis. Puede preceder hasta en 14 meses a otras manifestaciones de la dermatomiositis. En todos los casos, la miositis y la paniculitis presentan mejoría simultánea durante el tratamiento. Describimos una paciente de sexo femenino de 30 años que presenta lesiones clínica e histológicamente compatibles con paniculitis luego de 2 meses de que el compromiso muscular y cutáneo permitió el diagnóstico de dermatomiositis. Las lesiones cutáneas remitieron con el tratamiento esteroideo.Panniculitis is a rarely reported clinical finding in dermatomyositis. It may precede the other manifestations associated with dermatomyositis by as much as 14 months. In all cases, myositis and panniculitis improve simultaneously during treatment. The present report describes the case of a 30-year-old female patient with clinical and histopathological findings consistent with panniculitis two months after the onset of the muscle and cutaneous symptoms that permitted diagnosis of dermatomyositis. The skin lesions regressed following steroid treatment.

Hiperalgesia asociada al tratamiento con opioides

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A. Gil Martín; M. Moreno García; J. Sánchez-Rubio Ferrández; T. Molina García

2014-01-01

La hiperalgesia inducida por opioides es una reacción paradójica caracterizada por una percepción intensificada de dolor relacionada con el uso de estos medicamentos en ausencia de progresión de la enfermedad o de síndrome de retirada. A diferencia de los casos de tolerancia, definida como pérdida de potencia analgésica durante el uso prolongado de opioides, no se produce mejoría con el escalado de dosis. La hiperalgesia inducida por opioides se ha manifestado en pacientes con dosis de manten...

Paciente con tumor de cuerpo carotideo

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Mariuska Forteza Sáez

Full Text Available Los tumores de cuerpo carotideo (paragangliomas son neoplasias altamente vascularizadas, muy poco frecuentes y generalmente benignas, originadas en los quimiorreceptores del cuerpo carotideo. Se presenta el caso de un paciente de 54 años, con aumento de volumen cervical derecho, asintomático, con estudio preoperatorio y angiografía realizados por tomografía axial computarizada, que resultan compatibles con tumor de cuerpo carotideo. Se realiza disección subadventicial, informando la biopsia paraganglioma. El tumor fue completamente resecado, sin evidencia de recurrencia y sin complicaciones.

LINFOMA CUTÁNEO DE CÉLULAS B TIPO CENTRO FOLICULAR CON INFILTRACIÓN A MÉDULA ÓSEA: REPORTE DE UN CASO

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ARENAS SOTO, CLAUDIA MARCELA; MARIÑO ÁLVAREZ, MARÍA LILIANA; CALDERÓN GÓMEZ, JORGE ENRIQUE; GONZÁLEZ C, MARÍA ISABEL; ROBAYO, MARTHA PATRICIA

2012-01-01

Los linfomas cutáneos primarios de células B constituyen cerca del 2025% de todos los linfomas. El linfoma cutáneo primario de células B tipo centro folicular es el subtipo más frecuente y se manifiesta principalmente en pacientes adultos con una edad media de 58 años (1), la diseminación extracutánea es muy rara y se presenta con nódulos, tumores o placas solitarios o en grupo usualmente localizados en cabeza o tronco. Presentamos el caso de una paciente con un linfoma primario cutáneo tipo ...

Cerebral aspergillosis due to Aspergillus fumigatus in AIDS patient: first culture - proven case reported in Brazil Aspergilosis cerebral causada por Aspergillus fumigatus en paciente con SIDA: primer reporte de caso demostrado por cultivo en Brasil

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José E. Vidal

2005-06-01

Full Text Available Cerebral aspergillosis is a rare cause of brain expansive lesion in AIDS patients. We report the first culture-proven case of brain abscess due to Aspergillus fumigatus in a Brazilian AIDS patient. The patient, a 26 year-old male with human immunodeficiency virus (HIV infection and history of pulmonary tuberculosis and cerebral toxoplasmosis, had fever, cough, dyspnea, and two episodes of seizures. The brain computerized tomography (CT showed a bi-parietal and parasagittal hypodense lesion with peripheral enhancement, and significant mass effect. There was started anti-Toxoplasma treatment. Three weeks later, the patient presented mental confusion, and a new brain CT evidenced increase in the lesion. He underwent brain biopsy, draining 10 mL of purulent material. The direct mycological examination revealed septated and hyaline hyphae. There was started amphotericin B deoxycholate. The culture of the material demonstrated presence of the Aspergillus fumigatus. The following two months, the patient was submitted to three surgeries, with insertion of drainage catheter and administration of amphotericin B intralesional. Three months after hospital admission, his neurological condition suffered discrete changes. However, he died due to intrahospital pneumonia. Brain abscess caused by Aspergillus fumigatus must be considered in the differential diagnosis of the brain expansive lesions in AIDS patients in Brazil.La aspergilosis cerebral es una causa rara de lesión expansiva cerebral en pacientes con SIDA. Presentamos el primer reporte de un absceso cerebral causado por Aspergillus fumigatus en un paciente brasileño con SIDA. El paciente, de 26 años de edad, presentaba antecedentes de infección por el virus de la inmunodeficiencia humana (VIH, tuberculosis pulmonar y toxoplasmosis cerebral. Manifestó fiebre, tos, disnea y dos episódios de convulsiones. La tomografía computadorizada (TC demostró una lesión hipodensa parasagital y bi-parietal con

Beneficios de la terapia con resistómetro inspiratorio en los pacientes con esclerosis multiple frente a terapias respiratorias convencionales

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Martín Sánchez, Carlos

2016-01-01