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Sample records for c2b8 i-131 rituximab

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

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    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.

  2. High-dose radioimmunotherapy in refractory b-celI non-Hodgikin's lymphoma with I-131-labeled chimeric anti CD-20 C2B8 (I-131 rituximab): pilot trial

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    Kim, Sung Eun; Park, Yeon Hee; Cheon, Gi Jeong; Ryoo, Baek Yeol; Lee, Seung Sook; Choi, Chang Woon; Lim, Sang Moo [Korea Institute of Radiological and Medical Science, Seoul (Korea, Republic of)

    2004-07-01

    The native chimeric human-mouse anti CD-20 antibody IDEC-C2B8 (rituximab) is therapeutically applied in relapsed or refractory NHL. This ongoing pilot study was to evaluate whether high-dose radioimmunotherapy (RIT) with I-131 rituximab is therapeutically effective in refractory B-cell NHL. 5 patients (5 male, aged 50.89{+-}16.89) with chemorefractory NHL of B-cell origin (2 diffuse large B cell, 1 burkitt's lymphoma, and 2 mantle cell Iymphoma) oe, with a life expectancy of at least 3 months, and with a Kamofsky performance score of 60 and above were studied. The chimeric IgG1 anti CD 20 monoclonal antibody rituximab (mabthera, Roche) was radiolabelled with iodine-131 (I-131) using a modified chloaramine T method with high radiochemical purity (95%{+-}0.9) and preservation of immunoreactivity. All patients received therapeutic loading doses of unlabelled rituximab (18.5 MBq/kg) immediately prior to administration of therapeutic dose (3.7 GBq-8.5 GBq), and then underwent gamma camera scan and pre-and post-RIT FDG PET (within 7 day and day 30). Blood cell nadirs were reached at 2-3 weeks after therapy infusion, but all patients recovered at 6 weeks after treatment. Non hematologic toxicity was restricted to mild-to moderate nausea, fever, transient bilirubin, or liver enzyme elevation. Two (8.5 GBq) with mantle cell lymphoma and one with burkitt's lymphoma experienced good partial remissions, and one (5.5 GBq, DLBL) with bulky disease had a partial remission, and one patient (3.7 GBq, DLBL) with bulky disease had a mixed response. High-dose RIT with I-131 labelled rituximab seems to be effective and moderate toxicity. Further follow-up to monitor the long-term outcome are indicated.

  3. Biodistribution and kinetics of {sup 131}I-labelled anti-CD20 MAB IDEC-C2B8 (rituximab) in relapsed non-Hodgkin's lymphoma

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    Scheidhauer, Klemens; Wolf, Ingo; Baumgartl, Hans-Joachim; Reidel, Guenther; Schwaiger, Markus [Klinik und Poliklinik fuer Nuklearmedizin, Klinikum rechts der Isar, Technische Universitaet Muenchen, Ismaninger Strasse 22, 81675 Muenchen (Germany); Schilling, Christoph von; Schmidt, Burkhard; Peschel, Christian [III. Medizinische Klinik, Klinikum rechts der Isar, Technische Universitaet Muenchen (Germany)

    2002-10-01

    The native chimeric human-mouse anti-CD20 antibody IDEC-C2B8 (rituximab) is therapeutically applied in relapsed non-Hodgkin's lymphoma (NHL). The purpose of this study was to evaluate the distribution and pharmacokinetics of iodine-131 labelled rituximab in humans for radioimmunotherapy of relapsed CD20-positive NHL. Thirty-five patients with relapsed NHL were administered 20-40 mg rituximab labelled with 250 MBq {sup 131}I. Biodistribution was determined by the gamma camera whole-body scans, whole-body probe measurements and the analysis of serial blood and urine samples. Dosimetry was performed using the MIRDOSE 3 program. Antibody administration was well tolerated. The whole-body activity showed a mono-exponential decrease with a wide range of effective half-lives, the mean value (88 h) being significantly longer than the half-life of its murine counterpart, tositumomab. This led to appropriately higher dose factors for the whole body and organs. Activity was excreted mainly through the kidneys. Normal organs showed decreasing ratios of organ to whole-body activity over time, whereas the tumour tissue presented different kinetics, with increasing ratios of tumour to whole-body activity as evidence for specific antibody binding. It is concluded that {sup 131}I-labelled rituximab is suitable for pretherapeutic dosimetry. Due to the wide range of whole-body and organ dose factors, individual dosimetry is necessary for radioimmunotherapy with {sup 131}I-labelled rituximab. The therapeutic activities of {sup 131}I-labelled rituximab required to deliver similar doses should be lower than those of its murine counterpart. (orig.)

  4. Quantitative Analysis of High Dose Radioimmunotherapy with I-131 Anti-CD20 Monoclonal Antibody (Rituximab) in Patients with Non-Hodgkin's Lymphoma

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    Kim, Kyeong Min; Kang, Hye Jin; Choi, Tae Hyun; Cheon, Gi Jeong; Choi, Chang Woon; Lim, Sang Moo [Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of)

    2006-07-01

    Radioimmunotherapy (RIT) is therapeutic method for treatment of patient with incurable disease. I-131 is an radioisotope widely used for both diagnostic imaging and therapy, because of simultaneous emitting both gamma- and beta-ray. Recently, RIT using I-131 anti- CD20 rituximab has been introduced as one of the promising therapeutic model to treat patient with non- Hodgkin's Lymphoma (NHL). Although dosimetric approaches of low-dose I-131 rituximab imaging have been reported, there is no study of dosimetry with high dose imaging in patient with NHL yet. In this study, we evaluated strategy of high-dose RIT and investigated the kinetic behavior and absorbed dose to bone marrow and whole body in RIT study with high-dose strategy using I-131 rituximab for NHL.

  5. Assessment of absorbed dose and therapeutic response of tumor in repeated high-dose I-131 anti-CD20 monoclonal antibody (rituximab) radioimmunotherapy for non-Hodgkin's lymphoma

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    Byun, Byung Hyun; Lim, Sang Moo; Kim, Kyeong Min [Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of)] (and others)

    2007-07-01

    We assessed the therapeutic dose absorbed to the tumor and response in repeated RIT with I-131 rituximab for NHL. Patients with NHL (n=6) were administered a therapeutic dose of I-131 rituximab (192.527.0 mCi). The number of repeated administration was 3 for all patients. Total 12 measurable tumor regions were assessed at the time of each RIT. Whole-body (WB) planar images with anterior and posterior views were acquired sequentially at 5 min, 5hr, 24hr, 48hr, and 72hr post-injection using gamma camera. F-18-FDG PET/CT was performed before (within 7 days) and after (on Day 30) RIT. From PET/CT image acquired before RIT, maximum intensity projection (MIP) image of coronal view was acquired. Serial WB planar images were overlaid to the coronal MIP PET image, respectively, by means of registration using 4 fiducial marks (bilateral shoulder and buttock) implemented in AMIDE software. On registered MIP PET and WB planar images, both 2D-ROIs were drawn on the region of tumor and background nearby tumor. The shape of 2D-ROI of tumor was determined from the MIP PET image. The volume of tumor was measured from the CT image, the % change of tumor volume before and after RIT was used in evaluation of the therapeutic response. The values of CT-based tumor volume were 8.216.3cc. The values of absorbed dose for tumor and the % changes of tumor volume before and after RIT were 231.8603.0rad, and 55.548.7%, respectively, and did not show the linear relationship (r=0.2787). The values of absorbed dose for tumor and the % changes of tumor volume did not correlate with the number of repeated administration (p>0.05, ANOVA). Aligning PET and planar images could estimate the quantitative values of absorbed dose to tumor. The data suggest that repeated RIT with I-131 rituximab is necessary for NHL, because single-RIT is insufficient to achieve remission of disease.

  6. Get the Facts About Exposure to I-131 Radiation

    Science.gov (United States)

    ... test site fell over some parts of Utah, Colorado, Idaho, Nevada, and Montana. But I-131 traveled to all states, particularly those in the Midwestern, Eastern, and Northeastern United States. Some of the I-131 collected on pastures and on grasses. Depending on the location, grazing cows and goats ...

  7. Diagnosis of neuroblastoma with I-131 meta-iodobenzylguanidine scintigraphy

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    Odano, Ikuo; Ohsawa, Yoshihiro; Iwabuchi, Makoto; Sakai, Kunio; Hayashi, Mikio (Niigata Univ. (Japan). School of Medicine); Asami, Keiko; Utsumi, Jiro

    1991-01-01

    Pre- or post-operative I-131 meta-iodobenzylguanidine (I-131 MIBG) scans were reviewed for its diagnostic significance in neuroblastoma. The subjects were 18 patients with histologically proven neuroblastoma, who ranged in age from 6 months to 9 years. Abnormal uptake of I-131 MIBG was detected in all 10 patients showing positive urinary vanillylmandelic acid (VMA); there was a significant correlation between I-131 MIBG uptake and urinary VMA. For 10 patients undergoing preoperative I-131 MIBG scans, I-131 MIBG was taken up by primary tumors as small as one cm in diameter in 9 patients; the other one had negative urinary VMA. In detecting metastatic foci, the sensitivity of I-131 MIBG scans was 89% for the bone, 50% for the liver, 75% for the lymph nodes, and 38% for the bone marrow. In view of a high specificity, I-131 MIBG scintigraphy may be a useful approach to the localization of primary foci, as well as the diagnosis of metastasis and recurrence in neuroblastoma. (N.K.).

  8. Impact of reconstruction parameters on quantitative I-131 SPECT

    NARCIS (Netherlands)

    van Gils, C A J; Beijst, C; van Rooij, R; de Jong, H W A M

    2016-01-01

    Radioiodine therapy using I-131 is widely used for treatment of thyroid disease or neuroendocrine tumors. Monitoring treatment by accurate dosimetry requires quantitative imaging. The high energy photons however render quantitative SPECT reconstruction challenging, potentially requiring accurate cor

  9. Patterns of salivary gland uptake in I-131 MIBG scintigraphy.

    Science.gov (United States)

    Salanci, B Volkan; Ergün, E Lay

    2006-01-01

    I-131 MIBG scintigraphy is routinely used in the diagnosis of neuroendocrine tumours with high specificity. The radiopharmaceutical is taken up via uptake mechanism and actively transported into storage vesicules. The organs with dense sympathetic innervation such as salivary glands, heart, lachrymal glands, spleen and rarely adrenal medulla are normally visualized with I-131 MIBG. Asymetrical salivary gland uptake is important in a patient with suspected neuroendocrine tumours. Absence of radioactivity may be a result of sympathic denervation or tumor. Bilateral radioactivity absence is observed usually due to drugs or radiopharmaceutical storage conditions. Detailed examination of cervical region is crucial for localisation of neuroendocrine tumours. Therefore, possible false positives should be kept in mind.

  10. Does I-131-MIBG underestimate skeletal disease burden in neuroblastoma?

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    Barai Sukanta

    2004-10-01

    Full Text Available Background: Controversy persists as to the need for both MIBG and bone scanning in routine evaluation of neuroblastoma. Aim: To compare the efficacy of I-131- metaiodobenzylguanidine (MIBG scan against that of conventional Tc99m- methylene diphosphonate (MDP bone scan for the detection of skeletal deposition of neuroblastoma. Methods and Material: The study included 57 patients (36 boys, 21 girls: age range 1-14 years of neuroblastoma who underwent both bone scan with Tc99m-MDP and I-131-MIBG scan within 15 days of each other at presentation and during follow-up. Results: At presentation 11(19.2% patients had evidence of skeletal metastases on MDP scan against 7 patients who showed bony secondaries on MIBG scan. Of the 7 patients, with positive MIBG and MDP scans, MDP scan detected 11 sites whereas MIBG scan detected 7 sites. On follow-up study, 3 patients with initial abnormal MDP scan but normal MIBG scan, developed skeletal metastases detectable on MIBG scan, whereas 3 of the 46 patients who had normal MDP and MIBG scan at presentation; developed skeletal metastases detectable on MDP scan. MIBG scan was concordant in 2 of them but was normal in the third patient. Conclusion: I-131-MIBG underestimates skeletal disease burden in neuroblastoma. Therefore, Tc99m-MDP bone scan should remain a part of routine assessment of patients with neuroblastoma.

  11. Rituximab Injection

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    ... cells that normally fights infection) and chronic lymphocytic leukemia (CLL; a type of cancer that begins in ... fetus. You should use birth control to prevent pregnancy during your treatment with rituximab and for up ...

  12. Bioassay program: determination of I-131 body burden among radiation workers and nuclear medicine laboratory technicians

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    Duran, E.B.; Napenas, D.; San Jose, V.; Juan, N.

    The body burden of I-131 was determined among the radiation workers of the Philippine Atomic Energy Commission (PAEC) who are directly involved in I-131 processing and nuclear laboratory technicians of University of Santo Tomas and Veterans Hospital, who handle and dispense I-131 to patients. The routine monitoring was done by urine analysis. The untreated urine samples were counted directly for 4000 seconds using Nal(Tl) scintillation detector coupled to an ND66 microcomputer-based multichannel analyzer. Urine samples of radiation workers of PAEC who are not involved in I-131 processing and non-radiation workers were also assayed for comparison. For radiation workers of PAEC who are directly involved in processing I-131, the estimated body burden of I-131 ranged from <0.055 to 8.53 uCi (282 urine samples). These values were higher than those observed for radiation workers not involved in the handling or processing of I-131 with estimated body burden of I-131 ranging from <0.055 to 0.52 uCi (48 urine samples) or than those observed from non-radiation workers (<0.055 uCi). The maximum permissible burden of I-131 is 0.7 uCi.

  13. I-131 originating from nuclear medicine in German rivers; Nuklearmedizinisches {sup 131}I in deutschen Fluessen

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    Fischer, Helmut W. [Bremen Univ. (Germany). Fachbereich 1 - Physik; Strobl, Christopher [Bundesamt fuer Strahlenschutz, Oberschleissheim (Germany). Dienststelle Muenchen; Gellermann, Rainer

    2014-04-01

    The OSPAR agreement obligates the German government to determine and report the annual I-131 insertion from German rivers into the Northern Atlantic Ocean. In the frame of a research program the I-131 concentrations were determined in the rivers Elbe, Weser, Ems and Rhein that allowed the evaluation of the contamination load into the Northern Sea using a balance model.

  14. Phosphine-boranes as bidentate ligands: formation of [8,8-eta(2)-(eta(2)-(BH(3)).dppm)-nido-8,7-RhSB(9)H(10)] and [9,9-eta(2)-(eta(2)-(BH(3)).dppm)-nido-9,7,8-RhC(2)B(8)H(11)] from [8,8-(eta(2)-dppm)-8-(eta(1)-dppm)-nido-8,7-RhSB(9)H(10)] and [9,9-(eta(2)-dppm)-9-(eta(1)-dppm)-nido-9,7,8-RhC(2)B(8)H(11)], respectively.

    Science.gov (United States)

    Volkov, Oleg; Macías, Ramón; Rath, Nigam P; Barton, Lawrence

    2002-11-04

    The two clusters [8,8-(eta(2)-dppm)-8-(eta(1)-dppm)-nido-8,7-RhSB(9)H(10)] (1) and [9,9-(eta(2)-dppm)-9-(eta(1)-dppm)-nido-9,7,8-RhC(2)B(8)H(11)] (2) (dppm = PPh(2)CH(2)PPh(2)), both of which contain pendant PPh(2) groups, react with BH(3).thf to afford the species [8,8-eta(2)-(eta(2)-(BH(3)).dppm)-nido-8,7-RhSB(9)H(10)] (3) and [9,9-eta(2)-(eta(2)-(BH(3)).dppm))-nido-9,7,8-RhC(2)B(8)H(11)] (4), respectively. These two species are very similar in that they both contain the bidentate ligand [(BH(3)).dppm], which coordinates to the Rh center via a PPh(2) group and also via a eta(2)-BH(3) group. Thus, the B atom in the BH(3) group is four-coordinate, bonded to Rh by two bridging hydrogen atoms, to a terminal H atom, and to a PPh(2) group. At room temperature, the BH(3) group is fluxional; the two bridging H atoms and the terminal H atom are equivalent on the NMR time scale. The motion is arrested at low temperature with DeltaG++ = ca. 37 and 42 kJ mol(-1), respectively, for 3 and 4. Both species are characterized completely by NMR and mass spectral measurements as well as by elemental analysis and single-crystal structure determinations.

  15. Rituximab done

    DEFF Research Database (Denmark)

    Walker, Ulrich A; Jaeger, Veronika K; Chatzidionysiou, Katerina

    2016-01-01

    OBJECTIVE: To compare the effectiveness of biologics after rituximab (RTX) treatment in RA. METHODS: The effectiveness of TNF-α inhibitors (TNFi), abatacept (ABA) or tocilizumab (TCZ) was examined in patients previously treated with RTX using clinical data collected in the Collaborative Registries...... a greater decline of DAS28-ESR and clinical disease activity index than patients on TNFi (n = 89) or ABA (n = 90). This effect was also seen after adjusting for baseline prednisone use and the number of previous biologics. The mean DAS28-ESR scores in patients on TCZ were 1.0 (95% CI: 0.2, 1.7) and 1.8 (95......% CI: 1.0, 2.5) points lower than in patients on TNFi or ABA, respectively. In patients on TCZ, the clinical disease activity index was 9.4 (95% CI: 1.7, 16.1) and 8.1 (95% CI: 0.9, 15.3) points lower than on TNFi and ABA, respectively. Patients on TCZ more frequently had good EULAR responses than...

  16. Effects of Dosimetrically Guided I-131 Therapy on Hematopoiesis in Patients With Differentiated Thyroid Cancer.

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    Bikas, Athanasios; Schneider, Mark; Desale, Sameer; Atkins, Frank; Mete, Mihriye; Burman, Kenneth D; Wartofsky, Leonard; Van Nostrand, Douglas

    2016-04-01

    A retrospective analysis was performed to evaluate the effects of dosimetrically-guided I-131 treatment on hematopoiesis. Statistically significant decreases in CBC parameters following a specific time-pattern were shown.

  17. Role of gambogic acid and NaI131 in A549/DDP cells

    Science.gov (United States)

    Huang, Jing; Zhu, Xiaoli; Wang, Huan; Han, Shuhua; Liu, Lu; Xie, Yan; Chen, Daozhen; Zhang, Qiang; Zhang, Li; Hu, Yue

    2017-01-01

    Resistance to platinum in tumor tissue is a considerable barrier against effective lung cancer treatment. Radionuclide therapy is the primary adjuvant treatment, however, the toxic side effects limit its dosage in the clinical setting. Therefore, the present study aimed to determine whether an NaI131 radiosensitizer could help reduce the toxic side effects of radionuclide therapy. In vitro experiments were conducted to determine whether NaI131 can inhibit platinum resistance in A549/DDP cells, which are cisplatin-resistant non-small cell lung cancer cells, and whether gambogic acid (GA) is an effective NaI131 radiosensitizer. Cell proliferation following drug intervention was analyzed using MTT and isobolographic analysis. Apoptosis was assessed by flow cytometry. In addition, the mechanisms of drug intervention were analyzed by measuring the expression of P-glycoprotein (P-gP), B cell lymphoma 2 (Bcl-2), Bcl2-associated X protein (Bax) and P53 using western blot analysis and immunocytochemistry. According to isobolographic analysis, a low concentration of NaI131 combined with GA had a synergistic effect on the inhibition of A549/DDP cell proliferation, which was consistent with an increased rate of apoptosis. Furthermore, the overexpression of Bax, and the downregulation of P-gP, P53 and Bcl-2 observed demonstrated the potential mechanism(s) of NaI131 and GA intervention. NaI131 may induce apoptosis in A549/DDP cells by regulating apoptosis-related proteins. A low concentration combination of NaI131 and GA was able to significantly inhibit A549/DDP cell proliferation and induce cell apoptosis. Thus, the two drugs appear to have a synergistic effect on apoptosis of A549/DDP cells. PMID:28123519

  18. Unexpected Uptake by the Gallbladder in Post-Ablative I-131 Scan

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    Kemal Ünal

    2015-06-01

    Full Text Available A 47-year-old woman was diagnosed as papillary thyroid carcinoma. I-131 ablation therapy was applied following total thyroidectomy, and the whole-body scan revealed a focus of increased uptake in the right upper quadrant. Lateral view images of the uptake site showed that the focus was located near the right liver lobe. The patient was referred to radiology department for correlative abdominal Computed Tomography (CT and Ultrasonography (US to rule out a possible liver metastasis. CT images detected a gallstone in the corresponding area, which was verified by US. These methods did not reveal any metastatic disease in the liver or in other abdominal organs. This is the first published case report documents a rare false-positive finding of I-131 scan that was associated with an asymptomatic gallstone, and emphasizes the importance of correlative imaging in gallbladder related I-131 uptake.

  19. The value of detectable thyroglobulin in patients with differentiated thyroid cancer after initial I-131 therapy

    NARCIS (Netherlands)

    van Dijk, D.; Plukker, J. T. M.; van der Horst-Schrivers, A. N. A.; Jansen, L.; Brouwers, A. H.; Muller-Kobold, A.; Sluiter, W. J.; Links, T. P.

    2011-01-01

    Objective To assess the prognostic value of detectable thyroglobulin (Tg) after initial surgery and radioactive iodine (I-131) therapy by comparing patients with a negative post-therapeutic whole body scan (WBS) with either detectable or undetectable Tg. Background Differentiated thyroid cancer has

  20. Renal I-131-hippurate clearance overestimates true renal blood flow in the instrumented conscious dog

    NARCIS (Netherlands)

    Visscher, CA; DeZeeuw, D; Navis, G; VanZanten, AK; DeJong, PE; Huisman, RM

    1996-01-01

    We evaluated renal I-131-hippurate clearance (ERPF(hip)) as a measure of renal blood flow (RBF) in chronically instrumented conscious dogs. When adjusted for renal hippurate extraction (E(hip), 0.77 +/- 0.01) and hematocrit (Hct, 39.7 +/- 1%), calculated RBF(hip) (656 +/- 37 ml/min) markedly exceede

  1. Control system of liquid effluents generated in treatment with I-131; Sistema de control de efluentes liquidos generados en el tratamiento con I-131

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    Garcia M, T.; Ruiz C, M. A.; Angeles C, A.; Ramirez S, R., E-mail: teodoro.garcia@inin.gob.mx [ININ, Carretera Mexico-Toluca s/n, 52750 Ocoyoacac, Estado de Mexico (Mexico)

    2015-09-15

    In recent years, nuclear medicine has developed greatly in our country and around the world. Techniques for both medical diagnosis and therapy have increased the use of radiopharmaceuticals, notably the I-131. In Mexico there are around 150 nuclear medicine establishments authorized by the Comision Nacional de Seguridad Nuclear y Salvaguardias. Most of these establishments do not have an appropriate facility for the treatment of radioactive liquid effluents, to ensure compliance with the concentration limits established in the regulations. The Instituto Nacional de Investigaciones Nucleares (ININ) developed and implemented successfully, a control system of radioactive effluents (named SACEL) from a nuclear medicine facility. This system ensures an effective compliance with regulations and also better management and control of these radioactive effluents. Calculations and design of SACEL were made with respect to I-131, because is one of the most commonly used in radiotherapy and medical diagnostics, besides its half-life is greater in relation to other radionuclides. SACEL is comprised of four storage tanks and decay and a fifth tank for measuring the concentration of I-131 and later discharge to the drain; these tanks are connected to an automated system that controls the effluents passage. The calculation to determine the volume of the tanks was carried out according to the demand that has the hospital, to the maximum activity being poured in effluents and time required to decay. In this paper the design and installation of SACEL system, in addition to functioning as a facility that enables the Hospital meet the required standards is presented. Dose calculations performed with MCNPX and the methodology used in the calibration of the detection system is also presented. (Author)

  2. Development of gamma-photon/Cerenkov-light hybrid system for simultaneous imaging of I-131 radionuclide

    Science.gov (United States)

    Yamamoto, Seiichi; Suzuki, Mayumi; Kato, Katsuhiko; Watabe, Tadashi; Ikeda, Hayato; Kanai, Yasukazu; Ogata, Yoshimune; Hatazawa, Jun

    2016-09-01

    Although iodine 131 (I-131) is used for radionuclide therapy, high resolution images are difficult to obtain with conventional gamma cameras because of the high energy of I-131 gamma photons (364 keV). Cerenkov-light imaging is a possible method for beta emitting radionuclides, and I-131 (606 MeV maximum beta energy) is a candidate to obtain high resolution images. We developed a high energy gamma camera system for I-131 radionuclide and combined it with a Cerenkov-light imaging system to form a gamma-photon/Cerenkov-light hybrid imaging system to compare the simultaneously measured images of these two modalities. The high energy gamma imaging detector used 0.85-mm×0.85-mm×10-mm thick GAGG scintillator pixels arranged in a 44×44 matrix with a 0.1-mm thick reflector and optical coupled to a Hamamatsu 2 in. square position sensitive photomultiplier tube (PSPMT: H12700 MOD). The gamma imaging detector was encased in a 2 cm thick tungsten shield, and a pinhole collimator was mounted on its top to form a gamma camera system. The Cerenkov-light imaging system was made of a high sensitivity cooled CCD camera. The Cerenkov-light imaging system was combined with the gamma camera using optical mirrors to image the same area of the subject. With this configuration, we simultaneously imaged the gamma photons and the Cerenkov-light from I-131 in the subjects. The spatial resolution and sensitivity of the gamma camera system for I-131 were respectively ~3 mm FWHM and ~10 cps/MBq for the high sensitivity collimator at 10 cm from the collimator surface. The spatial resolution of the Cerenkov-light imaging system was 0.64 mm FWHM at 10 cm from the system surface. Thyroid phantom and rat images were successfully obtained with the developed gamma-photon/Cerenkov-light hybrid imaging system, allowing direct comparison of these two modalities. Our developed gamma-photon/Cerenkov-light hybrid imaging system will be useful to evaluate the advantages and disadvantages of these two

  3. Development of gamma-photon/Cerenkov-light hybrid system for simultaneous imaging of I-131 radionuclide

    Energy Technology Data Exchange (ETDEWEB)

    Yamamoto, Seiichi; Suzuki, Mayumi; Kato, Katsuhiko [Radiological and Medical Laboratory Sciences, Nagoya University Graduate School of Medicine (Japan); Watabe, Tadashi; Ikeda, Hayato; Kanai, Yasukazu [Department of Molecular Imaging in Medicine, Osaka University Graduate School of Medicine (Japan); Ogata, Yoshimune [Radiological and Medical Laboratory Sciences, Nagoya University Graduate School of Medicine (Japan); Hatazawa, Jun [Department of Molecular Imaging in Medicine, Osaka University Graduate School of Medicine (Japan)

    2016-09-11

    Although iodine 131 (I-131) is used for radionuclide therapy, high resolution images are difficult to obtain with conventional gamma cameras because of the high energy of I-131 gamma photons (364 keV). Cerenkov-light imaging is a possible method for beta emitting radionuclides, and I-131 (606 MeV maximum beta energy) is a candidate to obtain high resolution images. We developed a high energy gamma camera system for I-131 radionuclide and combined it with a Cerenkov-light imaging system to form a gamma-photon/Cerenkov-light hybrid imaging system to compare the simultaneously measured images of these two modalities. The high energy gamma imaging detector used 0.85-mm×0.85-mm×10-mm thick GAGG scintillator pixels arranged in a 44×44 matrix with a 0.1-mm thick reflector and optical coupled to a Hamamatsu 2 in. square position sensitive photomultiplier tube (PSPMT: H12700 MOD). The gamma imaging detector was encased in a 2 cm thick tungsten shield, and a pinhole collimator was mounted on its top to form a gamma camera system. The Cerenkov-light imaging system was made of a high sensitivity cooled CCD camera. The Cerenkov-light imaging system was combined with the gamma camera using optical mirrors to image the same area of the subject. With this configuration, we simultaneously imaged the gamma photons and the Cerenkov-light from I-131 in the subjects. The spatial resolution and sensitivity of the gamma camera system for I-131 were respectively ~3 mm FWHM and ~10 cps/MBq for the high sensitivity collimator at 10 cm from the collimator surface. The spatial resolution of the Cerenkov-light imaging system was 0.64 mm FWHM at 10 cm from the system surface. Thyroid phantom and rat images were successfully obtained with the developed gamma-photon/Cerenkov-light hybrid imaging system, allowing direct comparison of these two modalities. Our developed gamma-photon/Cerenkov-light hybrid imaging system will be useful to evaluate the advantages and disadvantages of these two

  4. [Novel uses of rituximab].

    Science.gov (United States)

    Frenzel, Laurent

    2013-12-01

    Since its approved by HAS in 1998, the use of rituximab increases every year. Marketed in France under the name MabThera, rituximab is used primarily in the treatment of B-cell malignancies including follicular lymphoma, diffuse large B-cell lymphoma and chronic lymphocytic leukemia and corresponding to the three main indications for treatment. However, given its action on B cells, rituximab also proves to be effective in rheumatoid arthritis. By extension as anti-B-cell, rituximab is actually used in other autoimmune diseases: in autoimmune cytopenias as idiopathic thrombocytopenic purpura and hemolytic anemia, in vasculitis, or multiple sclerosis, it is also used in organ transplantation as kidney in prophylaxy to rejection and treatment of EBV-mediated complications.

  5. Discovery – Development of Rituximab

    Science.gov (United States)

    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.

  6. Treatment of metastatic para-aortic paraganglioma by surgery, radiotherapy and I-131 mIBG

    Energy Technology Data Exchange (ETDEWEB)

    Ball, A.B.S.; Tait, D.M.; Fisher, C.; Sinnett, H.D.; Harmer, C.L. (Royal Marsden Hospital, London (United Kingdom))

    1991-10-01

    A patient with a malignant, functioning, aortico-sympathetic paraganglioma and a solitary bone metastasis causing paraplegia was treated by spinal decompression, irradiation of the metastasis, surgical excision of the primary tumour and systemic I-131 meta-iodobenzyl-guanidine (mIBG). Sixteen months after treatment there was no clinical, radiological or biochemical evidence of residual disease and neurological function was restored. The case supports the use of combined treatment incorporating mIBG in patients with metastatic neuroendocrine tumours which demonstrate mIBG uptake. (author).

  7. Calibration of the Accuscan II In Vivo System for I-131 Thyroid Counting

    Energy Technology Data Exchange (ETDEWEB)

    Orval R. Perry; David L. Georgeson

    2011-07-01

    This report describes the March 2011 calibration of the Accuscan II HpGe In Vivo system for I-131 thyroid counting. The source used for the calibration was an Analytics mixed gamma source 82834-121 distributed in an epoxy matrix in a Wheaton Liquid Scintillation Vial with energies from 88.0 keV to 1836.1 keV. The center of the detectors was position 64-feet from the vault floor. This position places the approximate center line of the detectors at the center line of the source in the thyroid tube. The calibration was performed using an RMC II phantom (Appendix J). Validation testing was performed using a Ba-133 source and an ANSI N44.3 Phantom (Appendix I). This report includes an overview introduction and records for the energy/FWHM and efficiency calibrations including verification counting. The Accuscan II system was successfully calibrated for counting the thyroid for I-131 and verified in accordance with ANSI/HPS N13.30-1996 criteria.

  8. Fetal radiation dose estimates for I-131 sodium iodide in cases where conception occurs after administration

    Energy Technology Data Exchange (ETDEWEB)

    Sparks, R.B.; Stabin, M.G. [Oak Ridge Inst. for Science and Education, TN (United States)

    1999-01-01

    After administration of I-131 to the female patient, the possibility of radiation exposure of the embryo/fetus exists if the patient becomes pregnant while radioiodine remains in the body. Fetal radiation dose estimates for such cases were calculated. Doses were calculated for various maternal thyroid uptakes and time intervals between administration and conception, including euthyroid and hyperthyroid cases. The maximum fetal dose calculating was about 9.8E-03 mGy/MBq, which occurred with 100% maternal thyroid uptake and a 1 week interval between administration and conception. Placental crossover of the small amount of radioiodine remaining 90 days after conception was also considered. Such crossover could result in an additional fetal dose of 9.8E-05 mGy/MBq and a maximum fetal thyroid self dose of 3.5E-04 mGy/MBq.

  9. Medically-derived I-131: a potential tool for understanding the fate of wastewater nitrogen in aquatic systems

    Science.gov (United States)

    Rose, P. S.; Smith, J. P.; Aller, R. C.; Cochran, J. K.; Swanson, R. L.; Murthy, S. N.; Coffin, R. B.

    2010-12-01

    Iodine-131(t1/2 = 8 days) has been measured in Potomac River water and sediments in the vicinity of the Blue Plains Water Pollution Control Plant (WPCP), Washington, DC. The source of I-131 is medical, where it is commonly used to treat thyroid cancer and hyperthyroidism. Iodine is metabolized by patients and eliminated primarily in urine. While other medical radioisotopes may enter the environment via sewage effluent, the nature and quantity of treatments using I-131 cause it to account for much of the radioactivity in sewage effluent. Natural iodine in aquatic systems is biologically cycled similar to other nutrients, such as nitrogen. Iodine-131 concentrations measured in sewage effluent from Blue Plains WPCP and in the Potomac River suggest a relatively continuous discharge of this isotope. Dissolved I-131 shows a strong, positive correlation with δ15N values of nitrate in the river. The range of I-131 concentrations detected in surface waters is 0.18 ± 0.01 to 0.68 ± 0.02 Bq/L. Surface water δ15NO3 values ranged from 8.7 ± 0.3 to 33.4 ± 7.3 ‰ with NO3+NO2 concentrations between 0.38 ± 0.02 and 2.79 ± 0.13 mgN/L. Sediment profiles of particulate I-131 and δ15N indicate rapid mixing or sedimentation and in many cases remineralization of a heavy nitrogen source consistent with wastewater nitrogen. Iodine-131 concentrations in sediments ranged from 1.31 ± 0.8 to 117 ± 2 Bq/kg dry weight. Values of δ15N in sediments ranged from 4.7 ± 0.1 ‰ to 9.3 ± 0.1 ‰. We propose that I-131 coupled with δ15N can be an excellent tracer for the short-term fate of wastewater nitrogen in this system. However, the utility of I-131 as a tracer is not limited to use in the Potomac River. Other studies have documented the presence of I-131 in several aquatic systems and continuous discharges of this radioisotope in sewage effluent are likely to be widespread in urban environments.

  10. Iodine-131 metaiodobenzylguanidine (I-131 MIBG) diagnosis and therapy of pheochromocytoma and paraganglioma: current problems, critical issues and presentation of a sample case.

    Science.gov (United States)

    Castellani, M R; Aktolun, C; Buzzoni, R; Seregni, E; Chiesa, C; Maccauro, M; Aliberti, G L; Vellani, C; Lorenzoni, A; Bombardieri, E

    2013-06-01

    Iodine-131 metaiodobenzylguanidine (I-131 MIBG) has been used for the diagnosis and treatment of malignant pheochromocytomas (PHEO) and paragangliomas (PGL) since 1980's. Despite increasing amount of experience with iodine-131 (I-131) MIBG therapy, many important questions still exist. In this article, we will discuss the current problems learned from clinical experience in diagnosis and therapy of PHEO/PGL with I-131 MIBG, and present a sample case to emphasize the critical aspects for an optimal treatment strategy.

  11. Implementation of iodine biokinetic model for interpreting I-131 contamination in breast milk after the Fukushima nuclear disaster

    Science.gov (United States)

    Tani, Kotaro; Kurihara, Osamu; Kim, Eunjoo; Yoshida, Satoshi; Sakai, Kazuo; Akashi, Makoto

    2015-07-01

    After the accident at the Fukushima Daiichi Nuclear Power Plant run by Tokyo Electric Power Company in 2011, breast milk samples obtained from volunteers living in Fukushima and neighboring prefectures were examined and small amounts of I-131 (2.2-36.3 Bq/kg) were detected in some samples. In this work, the I-131 concentrations in breast milk from nursing mothers in Ibaraki prefecture were calculated based on the iodine biokinetic model during lactation together with time-variable intake scenarios by inhalation of ambient air and ingestion of tap water, using the authors’ code. The calculated I-131 concentrations in breast milk generally agreed with those measured for the volunteers. Based on the results, thyroid equivalent doses to breast-fed infants were estimated for each place of residence of the volunteers on the assumption that these infants consumed 800 ml of breast milk every day, resulting in 10-11 mSv for Mito and Kasama cities and 1.1-1.8 mSv for Tsukuba and Moriya cities. It was suggested that breast milk consumption could be a major contributor to internal dose of breast-fed infants in areas with mild I-131 pollution; however, further studies considering personal behavior surveys would be necessary to estimate individual doses.

  12. Implications of mediastinal uptake of I-131 with regard to surgery in patients with differentiated thyroid carcinoma

    NARCIS (Netherlands)

    Haveman, JW; Phan, HTT; Links, TP; Jager, PL; Plukker, JTM

    2005-01-01

    BACKGROUND. Findings of mediastinal uptake of I-131 after surgical treatment for differentiated thyroid carcinoma (DTC) are common, especially in young patients. Given the frequency of false-positive findings, a protocol for diagnostic and their- apeutic strategies would be useful. With the goal of

  13. I-131 therapy for hyperthyroidism in carbimazole induced acute aplastic anaemia

    Energy Technology Data Exchange (ETDEWEB)

    Jenkin, B.A.; Van Every, B.; Kelly, M.J. [Alfred Hospital, Prahran, VIC (Australia). Nuclear Medicine Department

    1998-06-01

    Full text: We present a case of a 39 year old previously well woman who developed carbimazole-induced acute aplastic anaemia. Following 6 weeks of carbimazole for Grave`s disease she presented with fever, sore throat and lethargy and was found to be pancytopaenic. Haemoglobin fell to 79g/l (normal>120g/l), neutrophils to an undetectable level and platelets to 4,000/ml (normal>150,000/ml). From the MIRD schema it was estimated that a therapeutic dose of 444 MBq (12mCi) to treat her hyperthyroidism would deliver a red marrow radiation dose of about 30 mSv, at least an order of magnitude below any expected demonstrable deleterious effect on the marrow. Subsequently a dose of 444 MBq of I-131 was given and within 2 weeks the marrow had begun to recover, eventually to normal. This case would support the use of 1-131 for hyperthyroidism in carbimazole-induced marrow aplasia, even in profoundly depressed marrow

  14. Empirical shielding design data for facilities administering I131 for thyroid carcinoma.

    Science.gov (United States)

    Groth, M J

    1998-12-01

    Retrospective review of the records for 434 post thyroidectomy patients receiving I131 therapy for thyroid carcinoma revealed approximately 75% of the patients were discharged within 48 hours and 90% within 72 hours. Criterion for discharge was an external radiation dose below 25 muSv/hr, measured at one metre anterior to the patient's neck. The time-averaged average dose rate one metre anterior to the neck of a typical patient during the isolation period was 72 muSv/hr, with 90% of the patients below 82 muSv/hr. After correcting for the effects of patient size and scatter, the effective design dose rate from a patient in an isolation room treating two or three patients/week is 105 muSv.m2.hr-1, or 75 muSv.m.hr-1 where only one patient is treated each week. Concrete is the most economical shielding material, with 190 mm filled concrete block walls and 150 mm concrete floors as the minimum recommended shielding for a radioiodine therapy suite. Additional shielding will be required if the suite adjoins (including areas immediately above and below) areas with a high occupancy factor.

  15. Long-term efficacy of current thyroid prophylaxis and future perspectives on thyroid protection during I-131-metaiodobenzylguanidine treatment in children with neuroblastoma

    NARCIS (Netherlands)

    Clement, S. C.; van Rijn, R. R.; van Eck-Smit, B. L. E.; van Trotsenburg, A. S. P.; Caron, H. N.; Tytgat, G. A. M.; van Santen, H. M.

    2015-01-01

    Purpose Treatment with I-131-MIBG is associated with significant thyroid damage. This study was undertaken to investigate the long-term efficacy of current thyroid prophylaxis, to explore the relationship between thyroid dysfunction and thyroid volume after exposure to I-131-MIBG and to evaluate the

  16. Summary of measurements for the activity density from I-131 for the period September 1950 to July 1951

    Energy Technology Data Exchange (ETDEWEB)

    Paas, H.J.; Soldat, J.K.

    1951-08-21

    This report summarizes the results of measurements for the activity density from I-131 during the period covering the installation of the silver reactors in the off-gas lines of the dissolvers in the separations areas. This period also represented a significant reduction in the cooling period of the irradiated metal which was involved in the dissolving process. The determination of the activity density from I-131 was accomplished by sampling various media which included direct sampling from the 200 West Area stack and sampling of the canyon air exit line, analysis of vegetation samples collected at several environmental locations, and the analysis of aerosol concentrations from samples collected with caustic scrubbers. The results of these various programs are discussed.

  17. Filter hurra: a method simple for delete artifacts of the collimator in picture planar with I-131; Filtro Hurra: un metodo sencillo para eliminar artefactos del colimador en imagen planar con I-131

    Energy Technology Data Exchange (ETDEWEB)

    Perez Garcia, H.; Barquero Sanz, R.; Cardenas Solano, A.

    2015-07-01

    This paper presents an analysis of the existing noise is performed on images taken by a gamma camera with high-energy collimator HE for I-131. Using the Fourier transform, dominant spatial frequencies shown in the picture next to white noise. It is demonstrated by these frequencies geometry They correspond to the spatial periodicity of the collimator itself. Finally, the use of a frequency filter that eliminates image artifacts that causes collimator, thus obtaining a cleaner image, in which to determine the FWHM and thus the size of the uptake is proposed. (Author)

  18. Diagnostic capabilities of I-131, TI-201, and Tc-99m-MIBI scintigraphy for metastatic differentiated thyroid carcinoma after total thyroidectomy.

    Directory of Open Access Journals (Sweden)

    Fujie,Shunji

    2005-06-01

    Full Text Available

    We investigated the diagnostic capabilities of I-131, Tl-201, and Tc-99m-MIBI (hexakis-2-methoxyisobutyl- isonitrile scintigraphy for thyroid cancer metastases after total thyroidectomy over the entire body and for every locus before and after thyroid bed ablation. After total thyroidectomy of thyroid cancer, 36 cases were subjected to I-131 treatment 64 times. They consisted of 17 men and 19 women with 31 papillary carcinomas and 5 follicular carcinomas. Their ages were 22--75(an average of 60.5+/-12.3 years. I-131 scintigraphy(I-131, Tl-201 scintigraphy(Tl-201, and Tc-99m- MIBI scintigraphy (Tc-99m-MIBI were performed. We defined the metastases as those cases in which serum thyroglobulin (Tgincreased significantly or in which we were able to prove the lesions on CT (computed tomography, MRI (magnetic resonance imaging or bone scintigram. Three radiology medical specialists visually evaluated each scintigram and calculated the sensitivity, specificity, and likelihood ratio. For whole-body sensitivity, both Tl-201 and Tc-99m-MIBI were high before ablation and I-131 was high after ablation. Before ablation, the negative likelihood ratio was less than 0.1 for Tl-201 and Tc-99m-MIBI, while the positive likelihood ratio was more than 10 for Tl-201. After ablation, the positive likelihood ratio for I-131, Tl-201, and Tc-99m-MIBI was more than 10. The sensitivity of the mediastinum was appropriate, except for I-131 before ablation, and the sensitivity of the lung before and after ablation was inferior for either tracer. The specificity of the cervix for I-131 before ablation was markedly deteriorated, but it increased after ablation.

  19. A Quantitative Evaluation of Hepatic Uptake on I-131 Whole-Body Scintigraphy for Postablative Therapy of Thyroid Carcinoma.

    Science.gov (United States)

    Nakayama, Michihiro; Okizaki, Atsutaka; Sakaguchi, Miki; Ishitoya, Shunta; Uno, Takahiro; Sato, Junichi; Takahashi, Koji

    2015-07-01

    This study aimed to determine clinical association between quantitative hepatic uptake on postablative whole-body scan (WBS) with differentiated thyroid cancer (DTC) prognosis. We analyzed 541 scans of 216 DTC patients who were divided into 3 groups based on radioactive iodine (I-131) WBS uptake and clinical follow-up: group 1 (completion of ablation), group 2 (abnormal uptake in the cervical region), and group 3 (abnormal uptake with distant metastases). For each group, we calculated the ratio of I-131 WBS hepatic uptake (H) to cranial uptake as background (B); this ratio was defined as H/B. Furthermore, we made a distinction between group 1, as having completed radioactive iodine therapy (RIT) (CR), and group 2 and 3, as requiring subsequent RIT (RR). The average H/B scores were 1.34 (median, 1.36; range 1.00-2.1) for group 1; 1.89 (median, 1.75; range 1.41-4.20) for group 2; and 2.09 (median, 1.90; range 1.50-4.32) for group 3. Bonferroni multiple comparisons revealed significant differences in H/B among these groups. The H/B of group 1 was significantly smaller than that of other 2 groups (P < 0.0001). The precise cutoff value of H/B for therapeutic effect was ≤1.5. Moreover, 159 of 160 scans in the CR and 375 of 381 patients in the RR were correctly diagnosed using this cutoff value in the final outcome of RIT, yielding a sensitivity, specificity, positive predictive value, and negative predictive value of 99.4%, 98.4%, 99.7%, and 96.3%, respectively. Increased hepatic uptake of I-131 on WBS may predict disease-related progression.

  20. Evaluation of detectors for blood bioanalysis in Lu-177 and I-131 therapies for bone marrow dosimetry; Avaliacao de detectores para bioanalise de sangue em terapias com Lu-177 and I-131 para dosimetria de medula ossea

    Energy Technology Data Exchange (ETDEWEB)

    Degenhardt, Amilie Louize

    2016-10-01

    The measures traceability is mandatory for minimizing uncertainties in internal dosimetry for radiopharmaceuticals clinical studies and ensures the quality of the standard. Equipment should have resolution and efficiency compatible with radionuclides energies and, additionally, be able to quantify variations in human bodies' activities samples since the initial administration near the minimum residual activities. For testing three equipment (ionization chamber Capintec 25R, sodium iodine scintillator LTI Genesys Gamma-1 and high hyperpure germanium detector Canberra), they were prepared Lu-177 and I-131 radiation sources simulating patient's blood samples activities by adopting the following hypothesis: (1) initial activities according the Brazilian protocols; (2) blood volume in the whole body (5.3 L for adult men and 1.4 L for 5 years-old children); (3) effective half-lives (1.61 h and 42.9 h for Lu-177 bi-exponential adjustment and 15.7 h for I-131 mono-exponential adjustment); (4) sampling between 30 min and 168 h; (v) blood density adjustments. The standard sources were measured in the secondary standard ionization chamber Centronics IG11 at the Laboratorio Nacional de Metrologia das Radiacoes Ionizantes. The Capintec ionization chamber efficiencies ranged, respectively for I-131 and Lu-177, between (111.58±0.02)% and (102.27±0.01)% and HPGe semiconductor detector efficiencies ranged, respectively, between (89.40±0.03)% and (87.80±0.04)%. For the NaI detector, when the Lu-177 sources were positioned inside the detector the efficiencies ranged between (12.66±0.01)% and (11.54± 0.07)% and when the sources were positioned at 5 cm and 10 cm from the detector the efficiencies decreased to less than 5%. For I-131 sources positioned inside the detector, the efficiencies ranged between (29.76±0.21)% and (30.20±0.04)% and they decreased to less than 5% when they were positioned at 5 cm and 10 cm from the detector (deviation greater than 95

  1. Synthesis and biodistribution studies of (I-131,125)-iodo- and (Se-75) seleno-ergoline derivatives

    Energy Technology Data Exchange (ETDEWEB)

    Sadek, S.A.; Basmadjian, G.P.

    1984-01-01

    Pergolide, a new synthetic ergoline, has been shown to be a very potent dopamine agonist and to bind specifically to dopamine receptor sites in the brain. Two pergolide analogs labeled with I-125/I-131 and Se-75 were prepared. The radioactive iodoergoline derivative (Ia/Ib) was synthesized in a 100% yield by refluxing the mesyl derivative with NaI(125/131) in acetone. The (Se-75)-Selenopergolide derivative (II) was prepared in 80% radiochemical yield starting with (Se-75) selenious acid. Biodistribution studies of Ia and II in mature male rats showed relatively high uptake by the adrenals and brain (%dose/gm, range of 3 rats). Sequential images of dogs with Ib and II showed fast brain uptake with good retention for at least 20 min. Studies are in progress to evaluate the mechanism of uptake of Ib and II in rat and dog brains.

  2. Second malignancies in patients with differentiated thyroid carcinoma treated with low and medium activities of radioactive I-131

    Science.gov (United States)

    PICIU, DOINA; PESTEAN, CLAUDIU; BARBUS, ELENA; LARG, MARIA IULIA; PICIU, ANDRA

    2016-01-01

    Background and aim This study aimed at determining whether there is a risk regarding the development of second primary malignancies after patient exposure to the low and medium radioiodine activity used during the treatment of differentiated thyroid cancers (DTC). Methods Second primary malignancies that occurred after DTC were detected in 1,990 patients treated between 1970 and 2003. The mean long-term follow-up period was 182 months. Results Radioiodine I-131was administrated at a mean dose of 63.2 mCi. There were 93 patients with at least one second primary malignancy. The relative risk of development of second malignancy in DTC patients was increased (pDTC, but not to exposure to the low and medium activities of radioiodine administered as adjuvant therapy. PMID:27547058

  3. Estimation of parameters biokinetics from the resolution of a model compartment for I-131. Application to a patient with thyroid carcinoma hemodialysis; Estimacion de parametros bioceniticos a partir de la resolucion de un modelo compartimental para I-131. Aplicacion a un paciente hemodializado con carcinoma de torioides

    Energy Technology Data Exchange (ETDEWEB)

    Garcia, R.; Jimenez Feltstrom, D.; Luis dimon, F. J.; Sanchez Carmona, G.; Herrador Cordoba, M.

    2013-07-01

    This work aims to define a biokinetic model for the I-131, and solve it for different conditions of the patient or person affected (normal, with cancer of the thyroid or hyperthyroid). Solve the model in the case of a patient treated with I-131 for ablation of thyroid remnants with undergoing renal insufficiency and hemodialysis . Get the parameters Biokinetic this model for different situations. (Author)

  4. Vulvovaginal pyoderma gangrenosum secondary to rituximab therapy.

    Science.gov (United States)

    Dixit, Shreya; Selva-Nayagam, Priya; Hamann, Ian; Fischer, Gayle

    2015-01-01

    Rituximab is being used increasingly for the treatment of B-cell malignancies and nonmalignant conditions. Pyoderma gangrenosum is a rare neutrophilic dermatosis, which can be either idiopathic or associated with underlying systemic inflammatory conditions. We present a series of 4 patients who presented with ulcerative pyoderma gangrenosum in the vulvovaginal area after treatment with rituximab.

  5. TUMOR-LOCALIZATION WITH I-131-LABELED HUMAN-IGM MONOCLONAL-ANTIBODY 16.88 IN ADVANCED COLORECTAL-CANCER PATIENTS

    NARCIS (Netherlands)

    BOVEN, E; Haisma, Hidde; BRIL, H; MARTENS, HJM; VANLINGEN, A; DENHOLLANDER, W; KESSEL, MAP; DEJAGER, RL; ROOS, JC

    1991-01-01

    Human IgM monoclonal antibody 16.88 recognised an intracellular antigen strongly expressed in colorectal cancer tissue in 51% of our patients. Tumour localisation was carried out with 185 MBq I-131-16.88 (8 mg) in 20 of these patients with advanced disease. In 16 patients (80%) immunoscintigraphy wa

  6. Preoperative F-18-FDG PET for the detection of metastatic cervical lymph nodes in recurrent papillary thyroid carcinoma patients with negative I-131 whole body scans

    Energy Technology Data Exchange (ETDEWEB)

    Byun, Byung Hyun; Urn, Sang Moo; Cheon, Gi Jeong; Choi, Chang Woon; Lee, Byeong Cheol; Lee, Guk Haeng; Lee, Yong Sik; Shim, Youn Sang [Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of)

    2007-07-01

    We evaluated the diagnostic performance of FDG-PET for the detection of metastatic cervical lymph nodes in recurrent papillary thyroid carcinoma patients with negative I-131 scan. All patients had total thyroidectomy and following I-131 ablation therapy. In the follow-up period, FDG-PET showed suspected cervical lymph nodes metastases and neck dissection was performed within 3 months after FDG-PET. It had shown for all patients the negative I-131 scan within 3 months before FDG-PET or negative I-131 scan during the period of cervical lymph nodes metastases suspected on the basis of FDG-PET, CT, or ultrasonography until the latest FDG-PET. Preoperative FDG-PET results were compared with the pathologic findings of lymph nodes specimens of 19 papillary thyroid carcinoma patients. Serum Tg, TSH, and Tg antibody levels at the time of latest I-131 scan were reviewed. The size of lymph node was measured by preoperative CT or ultrasonography. In 45 cervical lymph node groups dissected, 31 lymph node groups revealed metastasis. The sensitivity and specificity of FDG-PET for metastasis were 74.2% (23 of 31) and 50.0% (7 of 14), respectively. Except for patients with elevated Tg antibody levels, all patients showed the elevated serum Tg levels than normal limits at the TSH of =30uIU/ml. 8 lesions without suspected metastatic findings on FDG-PET revealed metastasis (false negative), and none of them exceeded 8mm in size (4 to 8mm, median= 6mm). On the other hand, 23 true positive lesions on FDG-PET were variable in size (6 to 17mm, median=9mm). FDG-PET is suitable for the detection of metastatic cervical lymph nodes in patients with recurrent papillary thyroid carcinoma. However, false positive or false negative should be considered according to the size of lymph node.

  7. False Positive Findings on I-131 WBS and SPECT/CT in Patients with History of Thyroid Cancer: Case Series

    Science.gov (United States)

    Hannoush, Zeina C.; Palacios, Juan D.; Kuker, Russ A.

    2017-01-01

    Introduction. Although whole body scan (WBS) with I-131 is a highly sensitive tool for detecting normal thyroid tissue and metastasis of differentiated thyroid cancer (DTC), it is not specific. Additional information, provided by single photon emission computed tomography combined with X-ray computed tomography (SPECT/CT) and by the serum thyroglobulin level, is extremely useful for the interpretation of findings. Case Presentation. We report four cases of false positive WBS in patients with DTC: ovarian uptake corresponding to an endometrioma, scrotal uptake due to a spermatocele, rib-cage uptake due to an old fracture, and hepatic and renal uptake secondary to a granuloma and simple cyst, respectively. Conclusions. Trapping, organification, and storage of iodine are more prominent in thyroid tissue but not specific. Physiologic sodium-iodine symporter expression in other tissues explains some, but not all, of the WBS false positive cases. Other proposed etiologies are accumulation of radioiodine in inflamed organs, metabolism of radiodinated thyroid hormone, presence of radioiodine in body fluids, and contamination. In our cases nonthyroidal pathologies were suspected since the imaging findings were not corroborated by an elevated thyroglobulin level, which is considered a reliable tumor marker for most well-differentiated thyroid cancers. Clinicians should be aware of the potential pitfalls of WBS in DTC to avoid incorrect management. PMID:28246564

  8. Enfermedad pulmonar intersticial asociada a rituximab

    Directory of Open Access Journals (Sweden)

    Marcelo Fernández Casares

    2013-08-01

    Full Text Available La introducción en la práctica clínica del anticuerpo anti-CD20 rituximab ha mejorado sustancialmente el pronóstico de diversas enfermedades autoinmunes y hematológicas. Con el incremento de su uso ha aumentado el registro de efectos adversos, entre ellos la toxicidad pulmonar. Una de sus complicaciones más serias es la enfermedad pulmonar intersticial, entidad potencialmente fatal que debe ser considerada en pacientes que han recibido rituximab y presentan disnea, fiebre y tos sin clara evidencia de infección. Presentamos un caso de enfermedad pulmonar intersticial asociada a rituximab.

  9. Clinical Significance of Diffuse Intrathoracic Uptake on Post-Therapy I-131 Scans in Thyroid Cancer Patients

    Energy Technology Data Exchange (ETDEWEB)

    Choi, Hyun Su; Kim, Sung Hoon; Park, Sonya Youngju; Park, Hye Lim; Seo, Ye Young; Choi, Woo Hee [The Catholic Univ. of Korea, Suwon (Korea, Republic of)

    2014-03-15

    The purpose of this study was to identify the frequency and possible cause of diffuse intrathoracic uptake on post-therapy I-131 scans in thyroid cancer patients. We retrospectively reviewed 781 post-therapy scans of 755 thyroid cancer patients who underwent total thyroidectomy and radioactive iodine therapy between January and December 2010. Diffuse intrathoracic uptake on post-therapy scans was examined, and clinical patient characteristics including sex, age, regimen for thyroid-stimulating hormone (TSH) stimulation (thyroid hormone withdrawal or recombinant human TSH injection), TSH, thyroglobulin (Tg) and anti-thyroglobulin antibody (anti-Tg Ab) levels, therapeutic dose of radioactive iodine therapy and prior history of radioactive iodine therapy were recorded.Scan findings were correlated with chest CT, chest radiographs, laboratory tests and/or clinical status. Diffuse intrathoracic uptake without evidence of pathologic condition was categorized as indeterminate. The association between clinical characteristics and intrathoracic uptake were analyzed for negative intrathoracic uptake and indeterminate uptake groups. Diffuse intrathoracic uptake on post-therapy scans was demonstrated in 39 out of 755 (5.2 %) patients, among which 3 were confirmed as lung metastasis. The 14 patients that showed high Tg or anti-Tg Ab levels were considered to be at risk of having undetected micrometastasis on other imaging modalities. The remaining 22 were indeterminate (2.9 %). Upon comparison of negative intrathoracic uptake and indeterminate uptake groups, TSH stimulation by thyroid hormone withdrawal was shown to be significantly correlated with diffuse intrathoracic uptake (p <0.05). The frequency of diffuse intrathoracic uptake on post-therapy scans was 5.2 % and could be seen in thyroid cancer patients with underlying lung metastasis as well as those without definite pathologic condition. In the latter, there was a higher frequency for diffusely increased intrathoracic

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

    Energy Technology Data Exchange (ETDEWEB)

    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.)

  11. Tumor dosimetry for I-131 trastuzumab therapy in a Her2+ NCI N87 xenograft mouse model using the Siemens SYMBIA E gamma camera with a pinhole collimator

    Science.gov (United States)

    Lee, Young Sub; Kim, Jin Su; Deuk Cho, Kyung; Kang, Joo Hyun; Moo Lim, Sang

    2015-07-01

    We performed imaging and therapy using I-131 trastuzumab and a pinhole collimator attached to a conventional gamma camera for human use in a mouse model. The conventional clinical gamma camera with a 2-mm radius-sized pinhole collimator was used for monitoring the animal model after administration of I-131 trastuzumab The highest and lowest radiation-received organs were osteogenic cells (0.349 mSv/MBq) and skin (0.137 mSv/MBq), respectively. The mean coefficients of variation (%CV) of the effective dose equivalent and effective dose were 0.091 and 0.093 mSv/MBq respectively. We showed the feasibility of the pinholeattached conventional gamma camera for human use for the assessment of dosimetry. Mouse dosimetry and prediction of human dosimetry could be used to provide data for the safety and efficacy of newly developed therapeutic schemes.

  12. Rituximab-Induced Bronchiolitis Obliterans Organizing Pneumonia

    Directory of Open Access Journals (Sweden)

    Ahmet B. Ergin

    2012-01-01

    Full Text Available Rituximab-induced lung disease (R-ILD is a rare entity that should be considered in patients treated with rituximab who present with dyspnea, fever, and cough, but no clear evidence of infection. A variety of pathologic findings have been described in this setting. Bronchiolitis obliterans organizing pneumonia (BOOP is the most common clinicopathologic diagnosis, followed by interstitial pneumonitis, acute respiratory distress syndrome (ARDS, and hypersensitivity pneumonitis. Prompt diagnosis and treatment with corticosteroids are essential as discussed by Wagner et al. (2007. Here we present a case of an 82-year-old man who was treated with rituximab for recurrent marginal zone lymphoma. After the first infusion of rituximab, he reported fever, chills, and dyspnea. On computed tomography imaging, he was found to have bilateral patchy infiltrates, consistent with BOOP on biopsy. In our patient, BOOP was caused by single-agent rituximab, in the first week after the first infusion of rituximab. We reviewed the relevant literature to clarify the different presentations and characteristics of R-ILD and raise awareness of this relatively overlooked entity.

  13. A simple low-cost of liquid I-131 dispenser for routine radiopharmaceutical dispensing at nuclear medicine department, Institut Kanser Negara

    Energy Technology Data Exchange (ETDEWEB)

    Said, M. A.; Suhaimi, N. E. F. [Fakulti Sains dan Teknologi, Universiti Kebangsaan Malaysia, 43600 UKM, Bangi Selangor (Malaysia); Ashhar, Z. N., E-mail: aminhpj@gmail.com [Institut Kanser Negara, No 4, Jalan P7, Presint 7, 62250 Putrajaya (Malaysia); Zainon, R. [Advanced Medical & Dental Institute, Universiti Sains Malaysia, Bertam, 13200, Kepala Batas, Pulau Pinang (Malaysia)

    2016-01-22

    In routine radiopharmaceutical Iodine-131 ({sup 131}I) dispensing, the amount of radiation dose received by the personnel depends on the distance between the personnel and the source, the time spent manipulating the source and the amount of shielding used to reduce the dose rate from the source. The novel iRAD-I131 dispenser using recycle {sup 131}I liquid lead pot will lead into low cost production, less maintenance and low dose received by the personnel that prepared the {sup 131}I. The new fabricated of low cost {sup 131}I dispenser was tested and the dose received by personnel were evaluated. The body of lead material is made from 2.5 cm lead shielded coated with epoxy paint to absorb the radiation dose up to 7.4 GBq of {sup 131} I. The lead pot was supported with two stainless steel rod. The Optically Stimulated Luminescence (OSL) nanodot was used in this study to measure the dose rate at both extremities for every personnel who prepared the {sup 131}I. Each OSL nanodot was attached at the fingertip. Three different personnel (experienced between one to ten years above in preparing the radiopharmaceuticals) were participated in this study. The average equivalent dose at right and left hand were 122.694 ± 121.637 µSv/GBq and 77.281 ± 62.146 µSv/GBq respectively. This study found that the dose exposure received using iRAD-I131 was less up to seven times compared to the conventional method. The comparison of experimental data using iRAD-I131 and established radiopharmaceutical dispenser was also discussed. The innovation of {sup 131}I dispenser is highly recommended in a small radiopharmaceutical facility with limited budget. The novel iRAD-I131 enables implementation of higher output liquid dispensing with low radiation dose to the personnel.

  14. Preliminary report of a fetal-thyroid overexposure case due to the administration of I-131 during the second trimester of pregnancy

    Energy Technology Data Exchange (ETDEWEB)

    Gimenez, J.C. [Comision Nacional de Energia Atomica, Buenos Aires (Argentina); Sistema de Atencion Medica de Accidentados con Radiaciones Ionizantes (Argentina); Gutierrez, S.; Alcaraz, G. [Sistema de Atencion Medica de Accidentados con Radiaciones Ionizantes (Argentina)

    1992-07-01

    Sixty to eighty percent of patients with Graves's disease have antibodies directed against thyroglobulin or against thyroid microsomes. A contemporary interpretation is that thyroid stimulatory inmunoglobuline TSI mimics the action of TSH and stimulate the synthesis and release of thyroid hormone. In patient whose thyroids are capable of responding to such a trophic stimulus, TSI may be the mediator of hyperthyroxinemia. TSI cross the placenta and cause transient hyperthyroidism in some neonates (0,5-1 %) born to mothers who have high circulating levels of the antibodies. As regards adults aged 25 and up, administering I-131 radioactive iodine seems to be a satisfactory treatment for Graves' disease. Such a treatment, however, is to be avoided when treating either pregnant or breast-feeding women due to the effects that irradiation is likely to cause to the fetus or the suckling child. Even though such effects depend on the intrauterine developmental stage, the principal effects are as follows: (a) The embryo may be lethally affected; (b) Malformations and structure changes, or changes in the child's development are likely to occur; (3) The child may be mentally retarded; (4) An induction to cancer and leukemia is possible, and (e) Hereditary effect, may be expected. Moreover, it is a well-known fact that the fetal thyroid is able to capture and integrate iodine as of the 10th/12th gestation week. Thus, administering I-131 according to prescribed doses may define or suppress the thyroid function. Therefore, the highest precautions must be taken in order not to carelessly administer I-131 therapeutic doses to pregnant women. Any woman within the reproductive capacity range should be strongly advised that the pregnancy test is to be performed to avoid her fetus being irradiated. Precisely, the present paper deals with the inadvertent administering an I-131 therapeutic dose to pregnant woman with Graves disease whose child -unexpectedly enough- turned

  15. Tratamiento de la Enfermedad de Graves con I131: Primeros casos en la Unidad de Endocrinología Pediátrica del Hospital Nacional Cayetano Heredia, Lima-Perú.

    OpenAIRE

    SÁNCHEZ POVIS, Javier Ernesto; SANDOVAL OKUMA, José Carlos; CONTRERAS CARREÑO, Sara Elena; CABELLO MORALES, Emilio

    2012-01-01

    Objetivo: Describir la respuesta al tratamiento con I131 y sus complicaciones, en niños y adolescentes con enfermedad de Graves. Material y Métodos: Se estudiaron retrospectivamente las historias clínicas de los pacientes con diagnóstico de enfermedad de Graves y que recibieron tratamiento con I131 atendidos hasta 1999 en la Unidad de Endocrinología Pediátrica del Hospital Nacional Cayetano Heredia. Se registraron datos demográficos, peso tiroideo, captación de yodo, dosis de I131 recibida y ...

  16. Acquired Hemophilia A successfully treated with rituximab

    Directory of Open Access Journals (Sweden)

    Giovanni D'Arena

    2015-02-01

    Full Text Available Acquired hemophilia A (AHA is a rare bleeding disorder due to the development of specific autoantibodies against factor VIII. The anti-CD20 monoclonal antibody Rituximab has been proven to be effective in  obtaining a long-term suppression of inhibitors of AHA,  besides other immunosuppressive standard treatments. Here we describe a case of idiopathic AHA in a 60-year old man successfully treated with rituximab. He showed a complete clinical response with  a normalization of clotting  parameters after 5 weekly courses of rituximab given at a dose of 375 mg/sqm. , but after stopping rituximab, an initial worsening of coagulation  parameters  induced the addition of 3 further courses. At present, the patient is in complete clinical and hematological remission after 200 days.  This case confirms that Rituximab may be a safe and useful tool to treat AHA and, a prolonged administration can overcome the initial resistance. However, the precise position of this drug in the therapeutic strategy (first or second-line, alone or in combination with other drugs remains to be established and warrants further investigation.

  17. Rituximab in high-grade lymphoma.

    Science.gov (United States)

    Zwick, Carsten; Murawski, Niels; Pfreundschuh, Michael

    2010-04-01

    In 1997, the approval of the anti-CD20 antibody rituximab heralded a new era of combined immunochemotherapy for the treatment of malignant lymphoma. Until then, a combination of cyclophosphamide, vincristine, doxorubicin, and prednisone (CHOP) had been the standard of treatment for aggressive B-cell lymphoma for more than 25 years. The addition of rituximab led to an impressive improvement of response rates and survival outcomes in patients with follicular and diffuse large B-cell lymphoma (DLBCL) that has been confirmed in several randomized trials. Remaining challenges in the rituximab era are the identification of the optimal chemotherapy partner with respect to synergistic effects, as well as to the lack of interference with its effector mechanisms. Finally, the question of the optimal dosage and schedule of rituximab has to be addressed in well-designed randomized trials. The outcome of patients relapsing after a rituximab-containing induction regimen is dismal even with high-dose therapy and autologous stem cell transplantation (ASCT). For these patients new modalities of second-line therapy are urgently warranted.

  18. Rituximab use in the catastrophic antiphospholipid syndrome: descriptive analysis of the CAPS registry patients receiving rituximab.

    Science.gov (United States)

    Berman, Horacio; Rodríguez-Pintó, Ignasi; Cervera, Ricard; Morel, Nathalie; Costedoat-Chalumeau, Nathalie; Erkan, Doruk; Shoenfeld, Yehuda; Espinosa, Gerard

    2013-09-01

    The catastrophic variant of the antiphospholipid syndrome (APS) is characterized by thrombosis in multiple organs developing over a short period of time. First-line treatment for the catastrophic APS is the combination of anticoagulation plus corticosteroids plus plasma exchange and/or intravenous immunoglobulin. Despite this regimen, the mortality remains high and new treatment options are needed. By a systematic review of the Catastrophic APS Registry (CAPS Registry), we identified 20 patients treated with rituximab. The purpose of this study is to describe the clinical manifestations, laboratory features, and outcomes of rituximab-treated CAPS patients. In addition, the rationale for using rituximab in catastrophic APS is discussed.

  19. Software for dosimetry hypothyroid patients treated with I131 pick up and using probe gamma camera; Software para la dosimetria de pacientes hipertiroideos tratados con 131I utilizando sonda de captacion y gammacamara

    Energy Technology Data Exchange (ETDEWEB)

    Jimenez Felstrom, D.; Luis simon, J.; Reyes Garcia, R.; Derecho Torres, P.; Herrador Cordoba, M.

    2015-07-01

    In this communication the process recently implemented in our hospital for pre and post treatment of patients treated with I-131 in benign diseases of the thyroid gland internal dosimetry is described. We have developed a proprietary software that facilitates the process of dosimetry. Through scans Planar or pictures Spect be determines the mass of the gland thyroid. In function of the mass, is calculated by Monte Carlo the media power absorbed by disintegration of the I-131 in said gland endocrine. (Author)

  20. Enfermedad pulmonar intersticial asociada a rituximab

    OpenAIRE

    Marcelo Fernández Casares; Gisela Espósito; Alejandra González; Jaime Segovia; María de los Ángeles Galperín; Eduardo Del Valle

    2013-01-01

    La introducción en la práctica clínica del anticuerpo anti-CD20 rituximab ha mejorado sustancialmente el pronóstico de diversas enfermedades autoinmunes y hematológicas. Con el incremento de su uso ha aumentado el registro de efectos adversos, entre ellos la toxicidad pulmonar. Una de sus complicaciones más serias es la enfermedad pulmonar intersticial, entidad potencialmente fatal que debe ser considerada en pacientes que han recibido rituximab y presentan disnea, fiebre y tos sin clara evid...

  1. Rituximab Administration and Reactivation of HBV

    Directory of Open Access Journals (Sweden)

    Yutaka Tsutsumi

    2010-01-01

    Full Text Available Rituximab is a drug used for the treatment of B-cell non-Hodgkin's lymphoma, and its range of use has expanded to the treatment of collagen diseases such as idiopathic thrombocytopenic purpura and rheumatoid arthritis. One serious complication of rituximab use is the reactivation of dormant hepatitis B virus, and prevention of this phenomenon has become an urgent issue. This paper provides a general outline of the problem through an analysis of patient cases that we and other groups have experienced to date.

  2. Utility of SPECT/CT as an adjunct to planar whole body I-131 imaging: liver metastasis from papillary thyroid cancer.

    Science.gov (United States)

    Agriantonis, Demetrios J; Hall, Lance; Wilson, Michael A

    2009-04-01

    One of the major limitations of planar I-131 imaging is its lack of anatomic precision. SPECT/CT offers the benefit of precise anatomic localization that planar imaging lacks. Whether for confirmation of physiologic uptake or true pathology, SPECT/CT has an important role to play in clarifying equivocal findings. We present a case of papillary thyroid cancer metastatic to the liver, a relatively rare scenario. SPECT/CT allowed definitive lesion characterization at the time of the patient's visit to the nuclear medicine department.

  3. Rituximab induced hypoglycemia in non-Hodgkin's lymphoma

    Directory of Open Access Journals (Sweden)

    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.

  4. Long-Term Quality of Life and Pregnancy Outcomes of Differentiated Thyroid Cancer Survivors Treated by Total Thyroidectomy and I131 during Adolescence and Young Adulthood

    Directory of Open Access Journals (Sweden)

    Melanie Metallo

    2016-01-01

    Full Text Available Introduction. Differentiated thyroid cancer (DTC is rare and confers good prognosis. Long-term health related quality of life (HRQoL and pregnancy outcomes are not well known in subjects treated during adolescence and young adulthood. Methods. Cross-sectional analysis of HRQoL and global self-esteem, using SF-36 and ISP-25 surveys, and of pregnancy outcomes in female survivors of DTC treated by total thyroidectomy and I131 before age of 25 years. Results. Forty-five of 61 patients (74% responded to the survey. Cumulative I131 activity was ≤3.85 GBq in 18 subjects and >3.85 GBq in 27 subjects. Mean time from diagnosis was 7.6 ± 5.2 years for the group ≤ 3.85 GBq versus 16.9 ± 11.6 years for the group > 3.85 GBq (P 3.85 GBq and 10 in patients from the group ≤ 3.85 GBq. Frequency of miscarriages was of 17% (group > 3.85 GBq and 10% (group ≤ 3.85 GBq with 9 and 24 live births, respectively. No congenital malformations or first year mortality was noted. Conclusion. Long-term HRQoL, global self-esteem, and pregnancy outcomes are not affected in young female survivors of DTC.

  5. Long-Term Quality of Life and Pregnancy Outcomes of Differentiated Thyroid Cancer Survivors Treated by Total Thyroidectomy and I131 during Adolescence and Young Adulthood

    Science.gov (United States)

    Metallo, Melanie; Groza, Lelia; Brunaud, Laurent; Klein, Marc; Weryha, Georges; Feigerlova, Eva

    2016-01-01

    Introduction. Differentiated thyroid cancer (DTC) is rare and confers good prognosis. Long-term health related quality of life (HRQoL) and pregnancy outcomes are not well known in subjects treated during adolescence and young adulthood. Methods. Cross-sectional analysis of HRQoL and global self-esteem, using SF-36 and ISP-25 surveys, and of pregnancy outcomes in female survivors of DTC treated by total thyroidectomy and I131 before age of 25 years. Results. Forty-five of 61 patients (74%) responded to the survey. Cumulative I131 activity was ≤3.85 GBq in 18 subjects and >3.85 GBq in 27 subjects. Mean time from diagnosis was 7.6 ± 5.2 years for the group ≤ 3.85 GBq versus 16.9 ± 11.6 years for the group > 3.85 GBq (P 3.85 GBq and 10 in patients from the group ≤ 3.85 GBq. Frequency of miscarriages was of 17% (group > 3.85 GBq) and 10% (group ≤ 3.85 GBq) with 9 and 24 live births, respectively. No congenital malformations or first year mortality was noted. Conclusion. Long-term HRQoL, global self-esteem, and pregnancy outcomes are not affected in young female survivors of DTC. PMID:26977147

  6. Effects of bone marrow cell transplant on thyroid function in an I131-induced low T4 and elevated TSH rat model

    Directory of Open Access Journals (Sweden)

    Dávalos Alfredo

    2007-01-01

    Full Text Available Abstract Background We developed a study using low dose radioactive iodine creating an animal model of transient elevation of thyroid stimulating hormone (TSH. Male derived bone marrow cells were transplanted to asses their effect on thyroid function and their capability to repair the thyroid parenchyma. Results At 40 an 80 days after I131 treatment, the study groups TSH and T4 serum values both increased and decreased significantly respectively compared to the negative control group. Eight weeks after cell transplantation, neither TSH nor T4 showed a significant difference in any group. The mean number of SRY gene copies found in group I (Left Intracardiac Transplant was 523.3 and those in group II (Intrathyroid Transplant were only 73. Group III (No Transplant and IV had no copies. Group I presented a partial restore of the histological pattern of rat thyroid with approximately 20% – 30% of normal-sized follicles. Group II did not show any histological differences compared to group III (Positive control. Conclusion Both a significant increase of TSH and decrease of T4 can be induced as early as day 40 after a low dose of I131 in rats. Restore of normal thyroid function can be spontaneously achieved after using a low dose RAI in a rat model. The use of BM derived cells did not affect the re-establishment of thyroid function and might help restore the normal architecture after treatment with RAI.

  7. Normalization of lymphocyte count after high ablative dose of I-131 in a patient with chronic lymphoid leukemia and secondary papillary carcinoma of the thyroid: case report; Normalizacao da contagem de linfocitos apos dose ablativa de I-131 em um paciente com leucemia linfoide cronica e carcinoma papilifero da tireoide: relato de caso

    Energy Technology Data Exchange (ETDEWEB)

    Thom, Anneliese Rosmarie Gertrud Fischer; Hamerschlak, Nelson; Osawa, Akemi; Santos, Fabio Pires de Souza; Pasqualin, Denise da Cunha; Wagner, Jairo; Yamaga, Lilian Yuri Itaya; Cunha, Marcelo Livorsi da; Campos Neto, Guilherme de Carvalho; Funari, Marcelo Buarque de Gusmao, E-mail: afthom@einstein.br [Hospital Israelita Albert Einstein, Sao Paulo, SP (Brazil); Teles, Veronica Goes [Sociedade Brasileira de Diabetes, Sao Paulo, SP (Brazil)

    2014-07-01

    The authors report the case of a 70-year-old male patient with chronic lymphoid leukemia who presented subsequently a papillary carcinoma of the thyroid with metastases to regional lymph nodes. The patient was treated with surgical thyroidectomy with regional and cervical lymph node excision and radioiodine therapy (I-131). The protocolar control scintigraphy 4 days after the radioactive dose showed I-131 uptake in both axillae and even in the inguinal regions. PET/CT showed faint FDG-F-18 uptake in one lymph node of the left axilla. An ultrasound guided fine needle biopsy of this lymph node identified by I-131 SPECT/CT and FDG-F-18 PET/CT revealed lymphoma cells and was negative for thyroid tissue and thyroglobulin content. The sequential blood counts done routinely after radiation treatment showed a marked fall until return to normal values of leucocytes and lymphocytes (absolute and relative), which were still normal in the last control 19 months after the radioiodine administration. Chest computed tomography showed a decrease in size of axillary and paraaortic lymph nodes. By immunohistochemistry, cells of the lymphoid B lineage decreased from 52% before radioiodine therapy to 5% after the procedure. The authors speculate about a possible sodium iodide symporter expression by the cells of this lymphoma, similar to some other non-thyroid tumors, such as breast cancer cells. (author)

  8. Rituximab in treatment of idiopathic glomerulopathy

    Directory of Open Access Journals (Sweden)

    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

  9. I-131 Treatment of Graves' Disease in an Unsuspected First Trimester Pregnancy; the Potential for Adverse Effects on the Fetus and a Review of the Current Guidelines for Pregnancy Screening

    Directory of Open Access Journals (Sweden)

    Barrett Mark

    2010-03-01

    Full Text Available Graves' disease is a thyroid-specific autoimmune disorder in which the body makes antibodies to the thyroid-stimulating hormone receptor leading to hyperthyroidism. Therapeutic options for the treatment of Graves' disease include medication, radioactive iodine ablation, and surgery. Radioactive iodine is absolutely contraindicated in pregnancy as exposure to I-131 to the fetal thyroid can result in fetal hypothyroidism and cretinism. Here we describe a case of a female patient with recurrent Graves' disease, who inadvertently received I-131 therapy when she was estimated to be eight days pregnant. This was despite the obtaining of a negative history of pregnancy and a negative urine pregnancy test less than 24 hours prior to ablation. At birth, the infant was found to have neonatal Graves' disease. The neonatal Graves' disease resolved spontaneously. It was suspected that the fetal thyroid did not trap any I-131 as it does not concentrate iodine until 10 weeks of gestation.

  10. Update on the use of rituximab for intractable rheumatoid arthritis

    Directory of Open Access Journals (Sweden)

    R John Looney

    2009-07-01

    Full Text Available R John LooneyUniversity of Rochester, Rochester, New York, USAAbstract: It has been 3 years since rituximab, a mouse x human chimeric anti-CD20 monoclonal antibody that selectively depleted B cells, was approved by the FDA for the treatment of moderate to severe rheumatoid arthritis (RA with an inadequate response to anti-TNF therapies. Since approval rituximab has become a part of standard treatment, and additional data have become available on long-term efficacy and safety both from clinical trials and from post-marketing surveillance. In open long-term follow-up from clinical trials, patients treated with multiple courses of rituximab continued to respond in terms of signs and symptoms, and damage assessed radiographically was significantly inhibited. Moreover, the rate of serious infectious events was not increased as the number of courses increased. However, because of case reports of progressive multifocal leukoencephalopathy in patients treated with rituximab for non-malignant conditions, a black box warning has been added. Studies on the immunologic correlates of response to rituximab treatment including B cell subsets in peripheral blood and synovial biopsies are providing clues into how rituximab works for autoimmune disease. However, at this time we are not able to explain why some patients do not respond and cannot predict who will respond. Future challenges for the further development of rituximab for intractable RA will be discussed.Keywords: rheumatoid arthritis, rituximab, B cells, immunocompetency

  11. Rituximab treatment in patients with refractory inflammatory myopathies

    NARCIS (Netherlands)

    Mahler, E.A.; Blom, M.; Voermans, N.C.; Engelen, B.G. van; Riel, P.L. van; Vonk, M.C.

    2011-01-01

    Objective. To assess the efficacy of rituximab on disease activity and muscle strength in patients with inflammatory myopathies refractory to conventional therapy. Methods. Thirteen patients were treated with rituximab 1000 mg i.v., twice, with a 2-week interval and followed for a median of 27 month

  12. Rapid Infusion Rituximab for Maintenance Therapy: Is It Feasible?

    Directory of Open Access Journals (Sweden)

    Jolly Patel

    2013-01-01

    Full Text Available Rituximab is an anti-CD-20 monoclonal antibody used in the management of lymphoproliferative disorders. The use of maintenance rituximab has improved progression free survival and overall survival in follicular lymphomas. Although rapid rituximab infusions have been studied extensively, there is little data on the use of rapid infusions during maintenance therapy for low grade lymphomas. The primary objective of this retrospective analysis was to evaluate the incidence of Grade 3 and 4 toxicities with maintenance rapid infusion rituximab according to the Common Terminology Criteria for Adverse Events version 4 (CTC v. 4. Secondary objectives included evaluating all grade infusion related adverse events and correlation of adverse events with varying schedules of rituximab maintenance therapy. All patients who received rapid infusion rituximab as maintenance therapy for low grade lymphoma between December 2007 and November 2011 were included. Rapid rituximab infusions were administered over 90 minutes. Demographic, laboratory and clinical data were collected. A total of 109 patients received 647 rapid rituximab infusions. Three patients experienced an adverse reaction which resulted in one grade 1 infusion reaction and three grade 3 infusion reactions. No patients required hospitalization. All 3 patients received pharmacological and/or supportive care to relieve symptoms associated with the reaction.

  13. Low-dose rituximab is effective in pemphigus

    NARCIS (Netherlands)

    Horvath, B.; Huizinga, J.; Pas, H. H.; Mulder, A. B.; Jonkman, M. F.

    2012-01-01

    Background Rituximab, an anti-CD20 antibody, was shown in open series studies to be effective in treating pemphigus at a dose of 4 x 375 mg m(-2) as approved for B-cell malignancies. Objectives We investigated whether a lower dose of rituximab is also effective for pemphigus. Methods Patients with p

  14. A Case of Chronic Conjunctivitis following Rituximab Therapy

    Directory of Open Access Journals (Sweden)

    Marnelli A. Bautista

    2009-01-01

    Full Text Available The activity of the anti-CD20 monoclonal antibody, rituximab in B-cell non-Hodgkin's lymphoma, with relatively minimal toxicity has been well established. Adverse effects such as low-grade fever, urticaria, bronchospasm, sporadic tachycardia, and hypotension have been described. However, only a single case of rituximab-related, transient conjunctivitis has been documented in literature. We report an occurrence of chronic, bilateral conjunctivitis in an 88-year-old female diagnosed with stage IV, non-Hodgkin's lymphoma (NHL, who was maintained on rituximab for 12 months. In contrast to the previously described case, our patient developed severe conjunctival inflammation approximately three to four weeks following rituximab induction. Resolution of conjunctivitis occurred within two months after cessation of rituximab treatment.

  15. 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.

  16. The Effects of the Factors Related to the Patient and the Disease on the Performance of Ablation Therapy in Patients with Differentiated Thyroid Cancer who have Received I-131 Ablation Therapy

    Directory of Open Access Journals (Sweden)

    Tarık Şengöz

    2012-12-01

    Full Text Available Objective: To investigate whether the factors related to the patient and the disease have any effect on the success of ablation therapy in patients with differentiated thyroid cancer who have received I-131 ablation therapy. Material and Methods: All the patients with differentiated thyroid cancer were referred for I-131 ablation therapy after thyroidectomy between July 2007 and September 2009. The patients had at least six months of follow-up. Age, gender, type of tumor, presence of capsule invasion, size of tumor, number of the tumors, localization of the tumor, invasion of thyroid capsule, lymph/vessel invasion, presence of metastatic lymph nodes, type of surgery, preablation values of thyroglobulin (Tg, AntiTg, TSH, surveys for the evaluation of metastatic disease, (thyroid and bone scintigraphy, neck and abdominal ultrasonography, chest and brain computerized tomography, administered dose, postablation I-131 whole body scan (WBS and diagnostic I-131 WBS, neck USG, values of Tg and AntiTg at the 6th month were recorded. The presence of residual thyroid activity on the 6th month diagnostic I-131 WBS image was accepted as the criterion for ablation success. Results: 191 patients with differentiated thyroid cancer were assessed in this study. The overall success rate of the first ablation therapy was 74.3%. The success rate of the ablation therapy was 66% and 75% in metastatic group and non-metastatic group, respectively. Except the significant correlation between the number of pathologic lymph nodes and the success of ablation (p=0.025, there was no other significant correlation between the patient/disease related factors and the success of ablation therapy. Conclusion: Significant correlation between the number of the pathologic lymph nodes and the ablation therapy performance can also be due to statistical error because of the limited sample size. There was no significant correlation between other patient/disease related prognostic factors

  17. Fibrinogen labelling with I-131

    Energy Technology Data Exchange (ETDEWEB)

    Seminario, C.; Capillo, T.; Montanez, J. (Instituto Peruano de Energia Nuclear, Lima)

    1983-05-01

    Of the different techniques of labelling liophylized human fibrinogen, the technique of mono-chloride with modified iodine was selected. The labelling of the molecule was performed in alkali media of buffalo glycine in which the solution of stable iodine will react as well as on a later stage will the radioactive isotope. The labelling processes which were undertaken with different activities had an efficiency of over 40%; when purification with resins amberlite was carried through, in none of the cases were the impurities over 5%. Daily controls till the seventh day showed that the average values of radiochemical purity decrease were lower than 1%. The specific activity as well as the concentration of I/sup 131/, the fibrinogen and other characteristics come up to the norms of the pharmacopoeia which are applied.

  18. Experience of polymyositis and antisynthetase syndrome treatment with rituximab

    Directory of Open Access Journals (Sweden)

    S. G. Palshina

    2012-01-01

    Full Text Available The patient with polymyositis and antisynthetase syndrome treated with rituximab (Mabtera is described. Rituximab was added to thehigh‑dose cyclophosphamide therapy due to an acute onset of the disease with a highly progressive interstitial lung disease and inability of the high‑dose corticosteroids therapy because of comorbidity. There was almost complete normalization of pulmonary and muscular pathological changes with more than 4‑fold decrease of anti‑Jo‑1 antibodies on the treatment. No complications and no side effects during rituximab therapy were noted. This case report demonstrates the positive effect of rituximab in combination with high‑dose cyclophosphamide in the treatment of acute AS syndrome. The results published in literature are discussed.

  19. Prolonged Remission in Neuromyelitis Optica Following Cessation of Rituximab Treatment.

    Science.gov (United States)

    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.

  20. Rituximab-Associated Inflammatory Progressive Multifocal Leukoencephalopathy

    Science.gov (United States)

    Schofield, Christina; Harris, Penelope

    2016-01-01

    Progressive multifocal leukoencephalopathy (PML) is a rare disease of the immunosuppression that results from neurotropic invasion of the JC virus which leads to demyelination of oligodendrocytes. Immune reconstitution inflammatory syndrome (IRIS), on the other hand, is a condition of inflammation that develops as the immune system reconstitutes. This case report describes a case of a 35-year-old HIV-negative male who presented with three weeks of right lower extremity paresthesias as well as right upper extremity apraxia. He was diagnosed with PML complicated by IRIS secondary to Rituximab, which he had completed four months prior to presentation. Despite the condition's poor prognosis, the patient recovered with only minor deficits. PMID:27965904

  1. 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......, rheumatoid arthritis, and autoimmune hemolytic anemia. Recently, RTX has also been suggested for the treatment of certain connective tissue disease-related interstitial lung diseases (ILD) and hypersensitivity pneumonitis. Rare but serious pulmonary adverse reactions are reported. To raise awareness about...... this serious side effect of RTX treatment, as the indication for its use increases with time, we report five cases of probable RTX-ILD and discuss the current literature on this potentially lethal association....

  2. Rituximab: An emerging therapeutic agent for kidney transplantation

    Directory of Open Access Journals (Sweden)

    Joseph Kahwaji

    2009-10-01

    Full Text Available Joseph Kahwaji, Chris Tong, Stanley C Jordan, Ashley A VoComprehensive Transplant Center, Transplant immunology Laboratory, HLA Laboratory, Cedars-Sinai Medical Center, Los Angeles, CA, USAAbstract: Rituximab (anti-CD20, anti-B-cell is now emerging as an important drug for modification of B-cell and antibody responses in solid-organ transplant recipients. Its uses are varied and range from facilitating desensitization and ABO blood group-incompatible transplantation to the treatment of antibody-mediated rejection (AMR, post-transplant lymphoproliferative disorder (PTLD, and recurrent glomerular diseases in the renal allograft. Despite these uses, prospective randomized trials are lacking. Only case reports exist in regards to its use in de novo and recurrent diseases in the renal allograft. Recent reports suggests that the addition of rituximab to intravenous immunoglobulin (IVIG may have significant benefits for desensitization and treatment of AMR and chronic rejection. Current dosing recommendations are based on data from United States Food and Drug Administration-approved indications for treatment of B-cell lymphomas and rheumatoid arthritis. From the initial reported experience in solid organ transplant recipients, the drug is well tolerated and not associated with increased infectious risks. However, close monitoring for viral infections is recommended with rituximab use. The occurrence of progressive multifocal leukoencephalopathy (PML has been reported with rituximab use. However, this is rare and not reported in the renal transplant population. Here we will review current information regarding the effectiveness of rituximab as an agent for desensitization of highly human leukocyte antigen-sensitized and ABO-incompatible transplant recipients and its use in treatment of AMR. In addition, the post-transplant use of rituximab for treatment of PTLD and for recurrent and de novo glomerulonephritis in the allograft will be discussed. In

  3. Metabolomic profiling predicts outcome of rituximab therapy in rheumatoid arthritis

    OpenAIRE

    Sweeney, Shannon R; Kavanaugh, Arthur; Lodi, Alessia; Wang, Bo; Boyle, David; Tiziani, Stefano; Guma, Monica

    2016-01-01

    Objective: To determine whether characterisation of patients' metabolic profiles, utilising nuclear magnetic resonance (NMR) and mass spectrometry (MS), could predict response to rituximab therapy. 23 patients with active, seropositive rheumatoid arthritis (RA) on concomitant methotrexate were treated with rituximab. Patients were grouped into responders and non-responders according to the American College of Rheumatology improvement criteria, at a 20% level at 6 months. A Bruker Avance 700 M...

  4. Rituximab for children with immune thrombocytopenia: a systematic review.

    Directory of Open Access Journals (Sweden)

    Yi Liang

    Full Text Available BACKGROUND: Rituximab has been widely used off-label as a second line treatment for children with immune thrombocytopenia (ITP. However, its role in the management of pediatric ITP requires clarification. To understand and interpret the available evidence, we conducted a systematic review to assess the efficacy and safety of rituximab for children with ITP. METHODOLOGY/PRINCIPAL FINDINGS: We searched MEDLINE, EMBASE, Cochrane Library, CBM, CNKI, abstract databases of American Society of Hematology, American Society of Clinical Oncology and Pediatric Academic Society. Clinical studies published in full text or abstract only in any language that met predefined inclusion criteria were eligible. Efficacy analysis was restricted to studies enrolling 5 or more patients. Safety was evaluated from all studies that reported data of toxicity. 14 studies (323 patients were included for efficacy assessment in children with primary ITP. The pooled complete response (platelet count ≥ 100 × 10(9/L and response (platelet count ≥ 30 × 10(9/L rate after rituximab treatment were 39% (95% CI, 30% to 49% and 68% (95%CI, 58% to 77%, respectively, with median response duration of 12.8 month. 4 studies (29 patients were included for efficacy assessment in children with secondary ITP. 11 (64.7% of 17 patients associated with Evans syndrome achieved response. All 6 patients with systemic lupus erythematosus associated ITP and all 6 patients with autoimmune lymphoproliferative syndrome associated ITP achieved response. 91 patients experienced 108 adverse events associated with rituximab, among that, 91 (84.3% were mild to moderate, and no death was reported. CONCLUSIONS/SIGNIFICANCE: Randomized controlled studies on effect of rituximab for children with ITP are urgently needed, although a series of uncontrolled studies found that rituximab resulted in a good platelet count response both in children with primary and children secondary ITP. Most adverse events

  5. Severe Primary Raynaud's Disease Treated with Rituximab

    Science.gov (United States)

    Almoallim, Hani

    2016-01-01

    Raynaud's phenomenon refers to reversible spasms of the peripheral arterioles that can be primary Raynaud's phenomenon (PRP) or secondary Raynaud's phenomenon (SRP) to underlying connective tissue disease, both of which are characterized by a triphasic color response triggered by cold exposure or stress. PRP is typically a benign disease, whereas SRP may progress into digital ulcers and/or gangrene. Here, we report a case of a 55-year-old female diagnosed with PRP 7 years ago. Treatment with first-line agents, including calcium channel blocker, aspirin, and phosphodiesterase inhibitor, did not control her symptoms, which progressed to digital ulceration and gangrene. There were no symptoms of underlying autoimmune disease or malignancy, and autoimmune, serology, and immunology test results were normal; a biopsy of her left little finger was negative for vasculitis. Development to critical digital ischemia necessitated treatment with intravenous iloprost and heparin infusion followed by angioplasty, which led to a partial improvement. Due to persistent symptoms, rituximab therapy was initiated and two cycles induced a complete resolution of symptoms. PMID:27651971

  6. Cytomegalovirus enterocolitis in a patient with diffuse large B-cell lymphoma after chemotherapy with rituximab

    Institute of Scientific and Technical Information of China (English)

    Jason Seewoodhary

    2006-01-01

    Rituximab has been associated with the development of cytomegalovirus enterocolitis in immunosuppressed patients. A 51-year-old patient with diffuse large B-cell lymphoma who received a conditioning chemotherapy regimen (RCVP and RICE) consisting of rituximab before bone marrow transplantation went on to develop cytomegalovirus enterocolitis. This supports evidence from previously described cases that rituximab may be associated with cytomegalovirus enterocolitis.

  7. Organ S values and effective doses for family members exposed to adult patients following I-131 treatment: A Monte Carlo simulation study

    Energy Technology Data Exchange (ETDEWEB)

    Han, Eun Young [Department of Radiation Oncology, University of Arkansas Medical Sciences, Little Rock, Arkansas 72205 (United States); Lee, Choonsik [Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institute of Health, Bethesda, Maryland 20852 (United States); Mcguire, Lynn; Brown, Tracy L. Y. [Department of Radiology, Division of Nuclear Medicine, University of Arkansas Medical Sciences, Little Rock, Arkansas 72205 (United States); Bolch, Wesley E. [J. Crayton Pruitt Family Department of Biomedical Engineering, University of Florida, Gainesville, Florida 32611 (United States)

    2013-08-15

    Purpose: To calculate organ S values (mGy/Bq-s) and effective doses per time-integrated activity (mSv/Bq-s) for pediatric and adult family members exposed to an adult male or female patient treated with I-131 using a series of hybrid computational phantoms coupled with a Monte Carlo radiation transport technique.Methods: A series of pediatric and adult hybrid computational phantoms were employed in the study. Three different exposure scenarios were considered: (1) standing face-to-face exposures between an adult patient and pediatric or adult family phantoms at five different separation distances; (2) an adult female patient holding her newborn child, and (3) a 1-yr-old child standing on the lap of an adult female patient. For the adult patient model, two different thyroid-related diseases were considered: hyperthyroidism and differentiated thyroid cancer (DTC) with corresponding internal distributions of {sup 131}I. A general purpose Monte Carlo code, MCNPX v2.7, was used to perform the Monte Carlo radiation transport.Results: The S values show a strong dependency on age and organ location within the family phantoms at short distances. The S values and effective dose per time-integrated activity from the adult female patient phantom are relatively high at shorter distances and to younger family phantoms. At a distance of 1 m, effective doses per time-integrated activity are lower than those values based on the NRC (Nuclear Regulatory Commission) by a factor of 2 for both adult male and female patient phantoms. The S values to target organs from the hyperthyroid-patient source distribution strongly depend on the height of the exposed family phantom, so that their values rapidly decrease with decreasing height of the family phantom. Active marrow of the 10-yr-old phantom shows the highest S values among family phantoms for the DTC-patient source distribution. In the exposure scenario of mother and baby, S values and effective doses per time-integrated activity to

  8. Treatment of orbital inflammation with rituximab in Wegener's granulomatosis

    DEFF Research Database (Denmark)

    Baslund, Bo; Wiencke, Anne Katrine; Rasmussen, Niels;

    2012-01-01

    OBJECTIVES: To study the efficacy of rituximab therapy for the treatment of orbital inflammation in patients with Wegener's granulomatosis (WG). METHODS: Ten WG patients with orbital inflammation were included in this case-series. None had symptoms suggestive of extra-orbital disease activity....... Immunosuppressive medication (mycophenolate and prednisolone) was administered to 3 patients at the time of rituximab therapy. Three patients had previously been treated with anti-tumour-necrosis-factor-alpha antibodies, and one of these patients had also received cyclophosphamide as treatment for orbital...... inflammation. All patients were treated with 1000 mg of rituximab administered twice with an interval of 14 days between the infusions. Six months after therapy, a physical examination and a control computerised tomography (CT) scan was performed. RESULTS: All patients had orbital inflammation demonstrated...

  9. Hepatitis B virus reactivation with a rituximab-containing regimen

    Institute of Scientific and Technical Information of China (English)

    Yutaka; Tsutsumi; Yoshiya; Yamamoto; Shinichi; Ito; Hiroyuki; Ohigashi; Souichi; Shiratori; Hirohito; Naruse; Takanori; Teshima

    2015-01-01

    Rituximab is currently used not only in the treatment of B-cell lymphoma but also for various other diseases, including autoimmune diseases, post-transplant graft vs host disease, and rejection following kidney transplants. Due to rituximab’s widespread use, great progress has been made regarding research into complications that arise from its use, one of the most serious being the reactivation of hepatitis B virus(HBV), and efforts continue to establish guidelines for preventive treatment against this occurrence. This report discusses preventive measures against rituximab-induced HBV reactivation and future objectives.

  10. Research demystifies the interaction between Rituximab and its target

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    @@ As the first US FDA-approved monclonal antibody drug for the treatment of B-cell lymphomas and later on for the treatment of autoimmune diseases, Rituximab has been widely sold under the trade name of Rituxan ever since 1997 with an average sales volume over US$ 2 billion each year in the US.However, the recognition mechanism between Rituximab and its target CD20, an antigen expressed on the surface of mature B-cells, remained unclear. Now, an important step toward decoding the longstanding problem is achieved by scientists at the CAS Shanghai Institutes for Biological Sciences(SIBS) and their collaborators from the Second Military Medical University.

  11. Rituximab as a possible cause of posterior reversible encephalopathy syndrome

    Directory of Open Access Journals (Sweden)

    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.

  12. RITUXIMAB: NEW POTENTIALITIES OF THERAPY FOR RHEUMATOID ARTHRITIS

    Directory of Open Access Journals (Sweden)

    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.

  13. Rituximab-based immunosuppression for autoimmune haemolytic anaemia in infants.

    Science.gov (United States)

    Svahn, Johanna; Fioredda, Francesca; Calvillo, Michaela; Molinari, Angelo C; Micalizzi, Concetta; Banov, Laura; Schmidt, Madalina; Caprino, Daniela; Marinelli, Doretta; Gallisai, Domenico; Dufour, Carlo

    2009-04-01

    We report a case series of four infants with severe autoimmune haemolytic anaemia (AIHA) who responded to treatment with rituximab and cyclosporine after having failed first line therapy with high-dose steroid (prednisolone 4-8 mg/kg/d). Rituximab was started at 11-90 d from onset due to continued haemolysis; three infants also received cyclosporine A. Three of four infants reached complete response, defined as normal haemoglobin, reticulocytes and negative indices of haemolysis, at 7-21 months from diagnosis. In long-term follow-up two infants remained disease-free with normal immunology, one had undefined immunodeficiency and one had autoimmune lymphoproliferative syndrome.

  14. Comparison of 18F-FDG PET/CT, 99mTc-methy-isobutyl-isonitrile(MIBI) scan and radioiodine diagnostic whole body scan with I-131 post-therapeutic whole body scan in papillary thyroid carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Chung Ho; Park, Young Ha; Yoo, Ie Ryung; Kim, Sung Hoon; Chung, Soo Kyo [The Catholic University of Korea, Seoul (Korea, Republic of)

    2007-07-01

    To evaluate the usefulness of 18F-FDG PET/CT and 99mTc-MIBI scan in the detection of remnant thyroid tissue, recurrence or metastasis before high dose I-131 ablation therapy. Twenty-four patients (20 female, 4 male, age=52.913.2), who received 99mTc-MIBI scan, radioiodine diagnostic whole body scan (WBS) and 18F-FDG PET/CT within a week before high dose I-131 ablation therapy from May 2004 to September 2007 were retrospectively reviewed. All patients thyroid stimulating hormone, thyroglobulin (Tg) and anti-thyroglobulin level were checked before administering I-123 or I-131 for diagnostic WBS. TSH level were higher than 30 mIU/L in all patients. The radioiodine diagnostic WBS, 99mTc-MIBI scan and 18F-FDG PET/CT were compared with the post-therapeutic WBS obtain 7 days after administration of I-131 (=150 mCi). Post-therapeutic WBS of 4 patients showed distant metastases, commonly in lung, all 4 were positive on 18F-FDG PET/CT, 1 on 99mTc-MIBI scan, but none of them were detectable on radioiodine diagnostic WBS. 7 patients with cervical or supraclavicular lymph node metastases on post-therapeutic WBS, 5 were positive on 18F-FDG PET/CT, 4 on radioiodine diagnostic WBS, and 3 on 99mTc-MIBI scan. 9 patients with remnant thyroid tissue only in thyroid bed, 7 were positive on radioiodine diagnostic WBS, 5 on 18F-FDG PET/CT and 3 on 99mTc-MIBI scan. One case with high Tg level (>10ng/mI) was positive only on post-therapeutic WBS scan. 3 patients with high Tg level, all of diagnostic scans and post-therapeutic scan were negative. Compared to the post-therapeutic WBS with radioiodine diagnostic WBS, 99mTc-MIBI scan, 18F-FDG PET/CT, none of the studies were perfectly matched with post-therapeutic WBS, but can compensate each other. 18F-FDG PET/CT might be helpful, when lymph node or lung metastasis is suspected. Further evaluation with larger population is necessary.

  15. Rituximab-Based Treatment, HCV Replication, and Hepatic Flares

    Directory of Open Access Journals (Sweden)

    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.

  16. Failure of CHOP with rituximab for lymphomatoid granulomatosis

    NARCIS (Netherlands)

    Oosting-Lenstra, S. F.; Kooy, M. van Marwijk

    2007-01-01

    We present a 66-year-old male patient with pulmonary lymphomatoid granulomatosis. The patient had progressive disease after three courses of CHOP and rituximab and, therefore, treatment with interferon-alpha 2b 5 x 10(6) IE three times a week was started. This resulted in stable disease for five mon

  17. Rituximab for the treatment of patients with chronic lymphocytic leukemia

    Directory of Open Access Journals (Sweden)

    M Gentile

    2010-03-01

    Full Text Available M Gentile, E Vigna, C Mazzone, E Lucia, AG Recchia, L Morabito2, MG Bisconte, C Gentile, F Morabito1UOC di Ematologia, Azienda Ospedaliera di Cosenza, Italy; 2Servicio de Hematología y Hemoterapia, Hospital Universitario de Canarias, La Laguna, Tenerife, SpainAbstract: Chronic lymphocytic leukemia (CLL is a lymphoproliferative disorder that originates from antigen-experienced B lymphocytes that do not die and hence accumulate due to external survival signals or undergo apoptosis and are replenished by proliferating precursors. These neoplastic lymphocytes exhibit a characteristic immunophenotype of CD5+/CD19+/CD20+/HLA-DR+/CD23+/sIgdim. Thus, the CD20 antigen has been an appealing target for therapy. The introduction of the monoclonal antibody rituximab (anti-CD20 enabled an outstanding advance in CLL treatment. The introduction of this monoclonal antibody into chemotherapy regimens has dramatically improved complete response rates and progression-free survival in patients with both untreated and relapsed CLL. Although only preliminary data from phase III confirmatory trials have been reported, the FCR regimen, which combines fludarabine and cyclophosphamide with rituximab, is currently the most effective treatment regimen for CLL patients, and has also been demonstrated to significantly improve overall survival . The success of rituximab and the identification of other CLL lymphocyte surface antigens have spurred the development of a multitude of monoclonal antibodies targeting distinct proteins and epitopes in an attempt to target CLL cells more effectively.Keywords: rituximab, chronic lymphocytic leukemia, chemotherapy

  18. Rituximab treatment in rheumatoid arthritis: how does it work?

    NARCIS (Netherlands)

    Boumans, M.J.H.; Tak, P.P.

    2009-01-01

    Treatment with the chimerical monoclonal antibody rituximab results in CD20-directed B cell depletion. Although this depletion is almost complete in the peripheral blood of nearly all patients with rheumatoid arthritis, a proportion of patients does not exhibit a clinical response. The paper by Nako

  19. Rituximab (MabThera) til behandling af aktiv reumatoid artritis

    DEFF Research Database (Denmark)

    Fassi, Daniel El; 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...

  20. Allogeneic hematopoietic cell transplantation after conditioning with I-131-anti-CD45 antibody plus fludarabine and low-dose total body irradiation for elderly patients with advanced acute myeloid leukemia or high-risk myelodysplastic syndrome.

    Energy Technology Data Exchange (ETDEWEB)

    Pagel, John M.; Gooley, T. A.; Rajendran, Joseph G.; Fisher, Darrell R.; Wilson, Wendy A.; Sandmaier, B. M.; Matthews, D. C.; Deeg, H. Joachim; Gopal, Ajay K.; Martin, P. J.; Storb, R.; Press, Oliver W.; Appelbaum, Frederick R.

    2009-12-24

    We conducted a study to estimate the maximum tolerated dose (MTD) of I-131-anti-CD45 antibody (Ab; BC8) that can be combined with a standard reduced-intensity conditioning regimen before allogeneic hematopoietic cell transplantation. Fifty-eight patients older than 50 years with advanced acute myeloid leukemia (AML) or high-risk myelodysplastic syndrome (MDS) were treated with (131)I-BC8 Ab and fludarabine plus 2 Gy total body irradiation. Eighty-six percent of patients had AML or MDS with greater than 5% marrow blasts at the time of transplantation. Treatment produced a complete remission in all patients, and all had 100% donor-derived CD3(+) and CD33(+) cells in the blood by day 28 after the transplantation. The MTD of I-131-BC8 Ab delivered to liver was estimated to be 24 Gy. Seven patients (12%) died of nonrelapse causes by day 100. The estimated probability of recurrent malignancy at 1 year is 40%, and the 1-year survival estimate is 41%. These results show that CD45-targeted radiotherapy can be safely combined with a reduced-intensity conditioning regimen to yield encouraging overall survival for older, high-risk patients with AML or MDS. This study was registered at www.clinicaltrials.gov as #NCT00008177.

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

    Science.gov (United States)

    Schwarz, Anke; Wagner, A. D.; Haller, Hermann; Schiffer, Mario

    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.

  2. 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

    DEFF Research Database (Denmark)

    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 p...

  3. Tumour targeting and radiation dose of radioimmunotherapy with {sup 90}Y-rituximab in CD20+ B-cell lymphoma as predicted by {sup 89}Zr-rituximab immuno-PET: impact of preloading with unlabelled rituximab

    Energy Technology Data Exchange (ETDEWEB)

    Muylle, Kristoff [Vrije Universiteit Brussel, MIMA Research Group, Brussels (Belgium); Universite Libre de Bruxelles, Department of Nuclear Medicine, Jules Bordet Institute, Brussels (Belgium); Flamen, Patrick; Guiot, Thomas; Ghanem, Ghanem; Meuleman, Nathalie; Bourgeois, Pierre; Vanderlinden, Bruno; Vaes, Melanie; Bron, Dominique [Universite Libre de Bruxelles, Jules Bordet Institute, Brussels (Belgium); Vugts, Danielle J.; Dongen, Guus A.M.S. van [VU University Medical Centre, Amsterdam (Netherlands); Everaert, Hendrik [Vrije Universiteit Brussel, UZ Brussel, Brussels (Belgium); Vrije Universiteit Brussel, MIMA Research Group, Brussels (Belgium)

    2015-07-15

    To compare using immuno-PET/CT the distribution of {sup 89}Zr-labelled rituximab without and with a preload of unlabelled rituximab to assess the impact of preloading with unlabelled rituximab on tumour targeting and radiation dose of subsequent radioimmunotherapy with {sup 90}Y-labelled rituximab in CD20+ B-cell lymphoma. Five patients with CD20+ B-cell lymphoma and progressive disease were prospectively enrolled. All patients underwent three study phases: initial dosimetric phase with baseline {sup 89}Zr-rituximab PET/CT imaging without a cold preload, followed 3 weeks later by a second dosimetric phase with administration of a standard preload (250 mg/m{sup 2}) of unlabelled rituximab followed by injection of {sup 89}Zr-rituximab, and a therapeutic phase 1 week later with administration of unlabelled rituximab followed by {sup 90}Y-rituximab. PET/CT imaging and tracer uptake by organs and lesions were assessed. With a cold rituximab preload, the calculated whole-body dose of {sup 90}Y-rituximab was similar (mean 0.87 mSv/MBq, range 0.82-0.99 mSv/MBq) in all patients. Without a preload, an increase in whole-body dose of 59 % and 87 % was noted in two patients with preserved circulating CD20+ B cells. This increase in radiation dose was primarily due to a 12.4-fold to 15-fold higher dose to the spleen without a preload. No significant change in whole-body dose was noted in the three other patients with B-cell depletion. Without a preload, consistently higher tumour uptake was noticed in patients with B-cell depletion. Administration of the standard preload of unlabelled rituximab impairs radioconjugate tumour targeting in the majority of patients eligible for radioimmunotherapy, that is patients previously treated with rituximab-containing therapeutic regimens. This common practice may need to be reconsidered and further evaluated as the rationale for this high preload has its origin in the ''prerituximab era''. (orig.)

  4. Post-transplant lymphoproliferative disorder treated with rituximab: case report

    Institute of Scientific and Technical Information of China (English)

    MENG Hai-tao; LI Ying; LIU Jian-hua; XU Gai-xiang; TENG Xiao-dong

    2007-01-01

    @@ Post-transplant lymphoproliferative disorder (PTLD), a rare disease, is characterized by an abnormal proliferation of lymphoid cells after solid organ transplantation.1 This complication is usually caused by the immunosuppressive therapy following transplantation.Though the techniques of early detection and diagnosis of the disease are well established, treatment is not so straightforward and poses a real challenge. At this time,options include anti-viral therapy, cytotoxic chemotherapy, cellular immunotherapy, and reduction of immunosuppression. But the effects of these therapies are not satisfying. Rituximab, a chimeric monoclonal anti-CD20 antibody used for the treatment of B cell lymphoma with a good effect, is rarely, especially in combination with chemotherapy, used for PTLD. In this report, we describe a case of PTLD treated with rituximab and chemotherapy resulting in complete remission.

  5. Rituximab Efficacy during a Refractory Polyarteritis Nodosa Flare

    Directory of Open Access Journals (Sweden)

    Emmanuel Ribeiro

    2009-01-01

    Full Text Available Polyarteritis nodosa (PAN is a systemic vasculitis whose severe forms are treated with glucocorticoids and cyclophosphamide. Refractory patients are exposed to many complications, notably accelerated atherosclerosis. We report a case report of 71-year-old man followed for polyarteritis nodosa refractory to glucocorticoids and cyclosphosphamide. Systemic vasculitis relapses are followed to accelerated atherosclerosis: severe ischemic lesions led to amputation of lower limbs. Remission of refractory PAN is obtained with rituximab. Disappearance of biological inflammatory is allowed to regression of ischemic lesions in upper limbs. In this situation, we recommend a systematic vascular work-up for patients suffered from refractory vasculitis. On the other hand, therapeutic trials are needed to determine the real efficacy and place of rituximab in the treatment of polyarteritis nodosa.

  6. Randomised Phase I/II trial assessing the safety and efficacy of radiolabelled anti-carcinoembryonic antigen I131 KAb201 antibodies given intra-arterially or intravenously in patients with unresectable pancreatic adenocarcinoma

    Directory of Open Access Journals (Sweden)

    Bosonnet Lorraine

    2009-02-01

    Full Text Available Abstract Background Advanced pancreatic cancer has a poor prognosis, and the current standard of care (gemcitabine based chemotherapy provides a small survival advantage. However the drawback is the accompanying systemic toxicity, which targeted treatments may overcome. This study aimed to evaluate the safety and tolerability of KAb201, an anti-carcinoembryonic antigen monoclonal antibody, labelled with I131 in pancreatic cancer (ISRCTN 16857581. Methods Patients with histological/cytological proven inoperable adenocarcinoma of the head of pancreas were randomised to receive KAb 201 via either the intra-arterial or intravenous delivery route. The dose limiting toxicities within each group were determined. Patients were assessed for safety and efficacy and followed up until death. Results Between February 2003 and July 2005, 25 patients were enrolled. Nineteen patients were randomised, 9 to the intravenous and 10 to the intra-arterial arms. In the intra-arterial arm, dose limiting toxicity was seen in 2/6 (33% patients at 50 mCi whereas in the intravenous arm, dose limiting toxicity was noted in 1/6 patients at 50 mCi, but did not occur at 75 mCi (0/3. The overall response rate was 6% (1/18. Median overall survival was 5.2 months (95% confidence interval = 3.3 to 9 months, with no significant difference between the intravenous and intra-arterial arms (log rank test p = 0.79. One patient was still alive at the time of this analysis. Conclusion Dose limiting toxicity for KAb201 with I131 by the intra-arterial route was 50 mCi, while dose limiting toxicity was not reached in the intravenous arm.

  7. Rituximab-Induced Splenic Rupture and Cytokine Release

    Science.gov (United States)

    Nair, Ranjit; Gheith, Shereen; Lamparella, Nicholas

    2016-01-01

    Patient: Female, 55 Final Diagnosis: Mantle cell lymphoma Symptoms: Cytokine release syndrome • hypoglycemia • hypotension • splenic rupture • splenomegaly • vision loss Medication: — Clinical Procedure: Case Report Specialty: Oncology Objective: Unusual clinical course Background: Rituximab is a therapeutic monoclonal antibody that is used for many different lymphomas. Post-marketing surveillance has revealed that the risk of fatal reaction with rituximab use is extremely low. Splenic rupture and cytokine release syndrome are rare fatal adverse events related to the use of therapeutic monoclonal antibodies, especially in aggressive malignancies with high tumor burden. Case Report: A 55-year-old woman presented with abdominal pain and type B symptoms and was diagnosed with mantle cell lymphoma. Initial peripheral blood flow cytometry showed findings that mimicked features of chronic lymphocytic leukemia. Further treatment with rituximab led to catastrophic treatment complications that proved to be fatal for the patient. Conclusions: Severe cytokine release syndrome associated with biologics carries a very high morbidity and case fatality rate. With this case report we aim to present the diagnostic challenge with small B-cell neoplasms, especially mantle cell lymphoma and chronic lymphocytic lymphomas, and underscore the importance of thorough risk assessment for reactions prior to treatment initiation. PMID:26972227

  8. Rituximab in adult minimal change disease and focal segmental glomerulosclerosis.

    Science.gov (United States)

    Kronbichler, Andreas; Bruchfeld, Annette

    2014-01-01

    Treatment of nephrotic syndrome due to minimal change disease and focal segmental glomerulosclerosis remains a challenge since steroid dependence, steroid resistance and a relapsing disease course exhibits a high cumulative steroid dosage. The necessity of using alternative steroid-sparing immunosuppressive agents with potential toxic side effects also restricts their long-term use. Rituximab, a monoclonal antibody targeting CD20, has been increasingly used in the therapy of difficult-to-treat nephrotic syndrome. A clinical response has been shown for patients with steroid-dependent or frequently relapsing nephrotic syndrome, whereas the benefit seems to be limited in steroid-resistant patients, especially those with underlying focal segmental glomerulosclerosis. No potentially life-threatening adverse events have been observed in the treatment of adult minimal change disease and focal segmental glomerulosclerosis following rituximab administration. Since most reports are retrospective and evidence of efficacy is derived from small case series, more prospective trials in a controlled, randomized manner are highly desirable to delineate the use of rituximab or other B cell-depleting agents in steroid-dependent, frequently relapsing or steroid-resistant patients.

  9. Rituximab in the treatment of refractory lupus nephritis with vasculitis

    Directory of Open Access Journals (Sweden)

    Huseyin Kadikoy

    2012-01-01

    Full Text Available Dysfunction of the B lymphocyte, an important component of adaptive immunity, is thought to be important in the pathogenesis of lupus nephritis (LN. There are several novel strategies emerging including B-cell depletion by the monoclonal antibodies to B-cell markers, rituximab. We describe an unusual clinical response of a 22-year-old Hispanic woman with class IV LN with vasculitis while on dialysis to cyclophosphamide (CY and adjunct rituximab. The patient had a history of class III/V LN and was treated with nine months of CY and maintenance therapy with mycophenolate mofetil (MMF for three years. While on MMF, the patient deve-loped class IV LN with vasculitis leading to end-stage renal disease (ESRD. While the patient was on peritoneal dialysis, the patient was treated with two doses of rituximab and six doses of intravenous CY. The patient responded to this regimen and recovered kidney function within four months. The kidney function remained stable nine months after discontinuing peritoneal dialysis.

  10. Is rituximab effective for induction of remission in lupus nephritis?

    Directory of Open Access Journals (Sweden)

    Macarena Mac-Namara

    2014-08-01

    Full Text Available La combinación de ciclofosfamida y corticoides constituye el tratamiento estándar en pacientes con nefritis lúpica con indicación de terapia inmunosupresora mayor. Sin embargo, se asocia a importantes efectos adversos, por lo que existe interés en otros inmunosupresores como rituximab. Utilizando la base de datos Epistemonikos, la cual es mantenida mediante búsquedas en 19 bases de datos, identificamos 5 revisiones sistemáticas que en conjunto incluyen 24 estudios. Realizamos una síntesis mediante tablas de resumen de los resultados utilizando el método GRADE y concluimos que existe incertidumbre sobre la eficacia de rituximab en nefritis lúpica porque la certeza de la evidencia es muy baja, se asocia a efectos adversos importantes, y tiene alto costo. Rituximab no debiera utilizarse fuera de un estudio clínico, o sólo en casos en que otras alternativas han fracasado si es que no existen limitaciones de recursos.

  11. 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

    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...... were treated with rituximab plus methotrexate, 177 with rituximab plus leflunomide and 505 with rituximab alone. Significantly more patients achieved a European League Against Rheumatism good response at 6 months when treated with rituximab plus leflunomide (29.1%) compared with rituximab plus...... methotrexate (21.1%) and rituximab alone (19.3%; p=0.02 and p=0.01, respectively). Similar results were observed at 12 months. Adverse events occurred in 10.2%, 13.2% and 13.9% of patients on rituximab plus leflunomide, rituximab plus methotrexate and rituximab alone, respectively.CONCLUSIONS: Leflunomide...

  12. A single dose of rituximab does not deplete B cells in secondary lymphoid organs but alters phenotype and function

    NARCIS (Netherlands)

    Kamburova, E.G.; Koenen, H.J.P.M.; Borgman, K.J.; Berge, I.J. Ten; Joosten, I.; Hilbrands, L.B.

    2013-01-01

    A single dose of the anti-CD20 monoclonal antibody rituximab induces a nearly complete B cell depletion in peripheral blood, but not in secondary lymphoid organs. Modulation of this remaining B cell population due to rituximab treatment may contribute to the therapeutic effects of rituximab. To asse

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

    LENUS (Irish Health Repository)

    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.

  14. 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...

  15. The anti-CD20 antibody rituximab reduces the Th17 cell response

    NARCIS (Netherlands)

    Veerdonk, F.L. van de; Lauwerys, B.; Marijnissen, R.J.; Timmermans, K.; Padova, F.E. Di; Koenders, M.M.J.F.; Gutierrez-Roelens, I.; Durez, P.; Netea, M.G.; Meer, J.W. van der; Berg, W.B. van den; Joosten, L.A.B.

    2011-01-01

    OBJECTIVE: Rituximab has been shown to be successful in the treatment of rheumatoid arthritis (RA), and this unexpected finding indicates that B cells have an important role in this disease. The present study was undertaken to investigate the mechanism of action of rituximab in RA. METHODS: Twelve p

  16. In vitro effects of rituximab on the proliferation, activation and differentiation of human B cells.

    NARCIS (Netherlands)

    Kamburova, E.G.; Koenen, H.J.P.M.; Boon, L.; Hilbrands, L.B.; Joosten, I.

    2012-01-01

    Rituximab is a chimeric anti-CD20 monoclonal antibody (mAb) used in B-cell malignancies, various autoimmune disorders and organ transplantation. Although administration of a single dose of rituximab results in full B-cell depletion in peripheral blood, there remains a residual B-cell population in s

  17. 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 short

  18. T cells in tumors and blood predict outcome in follicular lymphoma treated with rituximab

    DEFF Research Database (Denmark)

    Wahlin, Björn Engelbrekt; Sundström, Christer; Holte, Harald;

    2011-01-01

    T cells influence outcome in follicular lymphoma, but their contributions seem to be modified by therapy. Their impact in patients receiving rituximab without chemotherapy is unknown.......T cells influence outcome in follicular lymphoma, but their contributions seem to be modified by therapy. Their impact in patients receiving rituximab without chemotherapy is unknown....

  19. Humoral responses after influenza vaccination are severely reduced in patients with rheumatoid arthritis treated with rituximab

    NARCIS (Netherlands)

    Van Assen, Sander; Holvast, Albert; Benne, Cornelis A.; Posthumus, Marcel D.; Van Leeuwen, Miek A.; Voskuyl, Alexandre E.; Blom, Marlies; Risselada, Anke P.; De Haan, Aalzen; Westra, Johanna; Kallenberg, Cornelis; Bijl, Marc

    2010-01-01

    Objective. For patients with rheumatoid arthritis (RA), yearly influenza vaccination is recommended. However, its efficacy in patients treated with rituximab is unknown. The objectives of this study were to investigate the efficacy of influenza vaccination in RA patients treated with rituximab and t

  20. Updated consensus statement on the use of rituximab in patients with rheumatoid arthritis

    DEFF Research Database (Denmark)

    Buch, Maya H; Smolen, Josef S; Betteridge, Neil;

    2011-01-01

    Since initial approval for the treatment of rheumatoid arthritis (RA), rituximab has been evaluated in clinical trials involving various populations with RA. Information has also been gathered from registries. This report therefore updates the 2007 consensus document on the use of rituximab...

  1. Tc-99m-labeled Rituximab for Imaging B Lymphocyte Infiltration in Inflammatory Autoimmune Disease Patients

    NARCIS (Netherlands)

    Malviya, G.; Anzola, K. L.; Podesta, E.; Lagana, B.; Del Mastro, C.; Dierckx, R. A.; Scopinaro, F.; Signore, A.

    2012-01-01

    The rationale of the present study was to radiolabel rituximab with 99m-technetium and to image B lymphocytes infiltration in the affected tissues of patients with chronic inflammatory autoimmune diseases, in particular, the candidates to be treated with unlabelled rituximab, in order to provide a r

  2. Updated consensus statement on the use of rituximab in patients with rheumatoid arthritis

    DEFF Research Database (Denmark)

    Buch, Maya H; Smolen, Josef S; Betteridge, Neil;

    2011-01-01

    Since initial approval for the treatment of rheumatoid arthritis (RA), rituximab has been evaluated in clinical trials involving various populations with RA. Information has also been gathered from registries. This report therefore updates the 2007 consensus document on the use of rituximab...... in the treatment of RA....

  3. 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 to...

  4. Rituximab for subcutaneous delivery: Clinical management principles from a nursing perspective.

    Science.gov (United States)

    Carlson, Julia; Cox, Keith; Bedwell, Kylie; Ku, Mathew

    2015-12-01

    Nurses play an integral role in administering treatments to patients with non-Hodgkin's lymphomas. Intravenous (IV) rituximab was approved by the Australian Therapeutic Goods Administration in 1998, and a novel subcutaneous (SC) formulation was approved in 2014. Fixed-dose SC rituximab is highly concentrated; co-formulation with a fully human recombinant vorhyaluronidase alfa enzyme helps overcome the physiological barriers of the SC space, facilitating drug dispersion. Despite a different pharmacokinetic profile to the IV preparation, SC rituximab demonstrates a comparable efficacy/safety profile. Most frequently occurring rituximab-related adverse events include neutropenia, nausea and constipation, and administration-related reactions are more frequent with the SC preparation. Compared with IV, SC delivery reduces treatment times and nurse workload, and patients report greater comfort and convenience. This article sets out nursing considerations for optimal administration of SC rituximab, including premedication, drug handling/preparation, injection technique, after-care and management of adverse events, particularly administration-related reactions.

  5. Rituximab therapy in Greek patients with rheumatoid arthritis

    Directory of Open Access Journals (Sweden)

    Haralampos M Moutsopoulos

    2008-10-01

    Full Text Available Aristotelis P Tsiakalos*, Nestor K Avgoustidis*, Haralampos M MoutsopoulosDepartment of Pathophysiology, Medical School, National Univercity of Athens, Athens, Greece. *These authors contributed equally to this workObjective: An open-label, prospective, uncontrolled study created to investigate clinical response, serological changes and side effects in Greek patients with rheumatoid arthritis (RA, after B-cell depletion with rituximab.Methods: Patients with high disease activity (disease activity score [DAS]-28 > 5.1 were selected for treatment with rituximab and received two infusions, 1 gr each, 2 weeks apart. Different disease parameters (visual analog scale, DAS-28, C-reactive protein [CRP], erythrocyte sedimentation rate, health assessment questionnaire, complement (C3, C4, rheumatoid factor [RF], anti-cyclic citrullinated peptide antibody [anti-CCP], swollen joint count, tender joint count, immunoglobulin M [IgM], IgG, IgA were performed at base line, 2, 4, and 6 months post-treatment. Response was defined according to the American College of Rheumatology (ACR criteria.Results: Seventeen patients received therapy. Treatment led to a reduction in various disease parameters. ACR20 was achieved in 41.11% of patients by week 8, 52.94% by week 16, and 82.35% by week 24. ACR50 was achieved in 5.88% by week 8, 41.17% by week 16, and 64.7% by week 24. ACR70 was achieved only by week 24 in 23.52% of patients. Statistical analysis has shown no differences in clinical response, between RF positive/negative patients, and anti-CCP-positive/negative patients, while decline of RF was better correlated with reduction of DAS-28 than with anti-CCP.Conclusions: Rituximab is a well tolerated and effective treatment in RA. Response was not correlated to RF or anti-CCP positivity. Decline of RF was associated with clinical response and reduction of DAS-28 and CRP.Keywords: rituximab, Greek patients, rheumatoid arthritis

  6. 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 a two-week interval and in combination with methotrexate. Mild to moderate side-effects are frequent, particularly during the first infusion, but long-term side-effects are generally rare, although pulmonary events and reactivation of viral infections of the liver is of concern....

  7. Should we consider MMF therapy after rituximab for nephrotic syndrome?

    Science.gov (United States)

    Filler, Guido; Huang, Shih-Han Susan; Sharma, Ajay P

    2011-10-01

    The management of steroid-dependent nephrotic syndrome, especially in patients who have failed to respond to cytotoxic drugs, such as cyclophosphamide, remains challenging. Rituximab represents a new (off-label) therapeutic option. In a significant portion of patients, it has a short serum half-life following the recovery of CD20-positive cells. The addition of mycophenolate mofetil (MMF) as a maintenance therapy is also an attractive option, but one which requires testing in a prospective randomized clinical trial with therapeutic drug monitoring and mechanistic ancillary studies.

  8. Radioactive Iodine (I-131) Therapy for Hyperthyroidism

    Science.gov (United States)

    ... treatment for an overactive thyroid, a condition called hyperthyroidism, and also may be used to treat thyroid ... treatment for an overactive thyroid, a condition called hyperthyroidism . Hyperthyroidism can be caused by Graves' disease, in ...

  9. Crescendo response to rituximab in oral pemphigus vulgaris: a case with 7-year follow-up.

    Science.gov (United States)

    Greenblatt, D T; Benton, E C; Groves, R W; Setterfield, J F

    2016-07-01

    Pemphigus vulgaris (PV) is an autoimmune blistering disease affecting the skin and mucous membranes. Rituximab, a CD20 chimeric monoclonal antibody, has efficacy in PV management. We report a case of severe oral PV that showed a progressive response to repeated courses of rituximab, culminating in a rapid response within 4 weeks following severe relapse 4 years after initial therapy. It demonstrates the progressively shorter time to achieve partial or complete remission following rituximab infusions, combined with minimal adjuvant therapy over a 7-year follow-up period.

  10. Rituximab in a child with autoimmune thrombotic thrombocytopenic purpura refractory to plasma exchange.

    Science.gov (United States)

    Narayanan, Parameswaran; Jayaraman, Aparna; Rustagi, Rashi S; Mahadevan, S; Parameswaran, Sreejith

    2012-07-01

    A nine-year-old girl presented with headache, purpura and mild left hemiparesis. Laboratory evaluation revealed thrombotic microangiopathy with ADAMTS13 deficiency, with auto-antibodies to ADAMTS13. She was treated with plasma exchange and steroids, following which she improved transiently, relapsing within 2 months. The relapse was refractory to conventional therapy and rituximab was tried. She had good response to rituximab and has been in remission for the past 12 months. Rituximab may be a promising option for children with acquired TTP refractory to plasma exchange and steroids.

  11. Rituximab versus cyclophosphamide in ANCA-associated renal vasculitis : 2-year results of a randomised trial

    NARCIS (Netherlands)

    Jones, Rachel B.; Furuta, Shunsuke; Tervaert, Jan Willem Cohen; Hauser, Thomas; Luqmani, Raashid; Morgan, Matthew D.; Peh, Chen Au; Savage, Caroline O.; Segelmark, Marten; Tesar, Vladimir; van Paassen, Pieter; Walsh, Michael; Westman, Kerstin; Jayne, David R. W.; Stegeman, C. A.

    2015-01-01

    Objectives The RITUXVAS trial reported similar remission induction rates and safety between rituximab and cyclophosphamide based regimens for antineutrophil cytoplasm antibody (ANCA)-associated vasculitis at 12months; however, immunosuppression maintenance requirements and longer-term outcomes after

  12. Induction treatment of previously undiagnosed ANCA-associated vasculitis in a renal transplant patient with Rituximab

    Science.gov (United States)

    Graham-Brown, M. P. M.; Aljayyousi, R.; Baines, R. J.; Burton, J. O.; Brunskill, N. J.; Furness, P.; Topham, P.

    2016-01-01

    We report the case of a 40-year-old female transplant patient with undiagnosed ANCA-associated vasculitis (AAV) and renal allograft dysfunction who achieved disease remission with restoration of transplant function following induction therapy with rituximab. There are currently no trial data looking at the use of rituximab for induction of remission of renal transplant patients with AAV. Although recurrence of AAV following renal transplantation is rare, such patients have invariably had multiple previous exposures to induction and maintenance immunosuppressive regimens, often limiting treatment options post-transplantation. In this case, rituximab was well tolerated with no side effects, and was successful in salvaging transplant function. Optimal treatment regimens for relapsed AAV in the transplant population are not known, and clinical trials are needed to evaluate the efficacy and safety of rituximab at inducing and maintaining disease remission in relapsed AAV following transplantation. PMID:27699052

  13. Rituximab in the treatment of refractory pemphigus vulgaris

    OpenAIRE

    Fernandes, I.; Sanches, M.; Velho, G; Selores, M.

    2012-01-01

    O pênfigo vulgar é uma doença bolhosa auto-imune rara, que atinge a pele e as mucosas. Geralmente tem um curso clínico severo, sendo necessário o recurso a terapêutica prolongada com corticóides sistémicos e outros fármacos imunossupressores, que podem conduzir a efeitos adversos graves. O rituximab é um anticorpo monoclo- nal quimérico dirigido ao antigénio CD20, expresso pelos linfócitos B. Recentemente, têm surgido alguns estudos que documentam o seu sucesso terapêutico no tratamento de pê...

  14. Rituximab induction therapy in highly sensitized kidney transplant recipients

    Institute of Scientific and Technical Information of China (English)

    YIN Hang; WAN Hao; HU Xiao-peng; LI Xiao-bei; WANG Wei; LIU Hang; REN Liang; ZHANG Xiao-dong

    2011-01-01

    Background The number of highly sensitized patients is rising, and sensitization can lead to renal transplant failure.The present study aimed to investigate the safety and efficacy of renal transplantation following induction therapy with rituximab in highly sensitized kidney transplant recipients.Methods Seven highly sensitized kidney transplant recipients who underwent rituximab therapy from December 2008 to December 2009 were retrospectively analyzed. There were 3 men and 4 women, with a mean age of 38.5 years (range, 21-47 years). The duration of hemodialysis was 3-12 months, with a mean duration of 11 months. For 4 patients,this was the second transplant; the previous graft survival time was 2-11 years, with a mean survival time of 5.8 years. All the female recipients had history of multiple pregnancies, and all patients had previously received blood transfusions. All donors were men, with a mean age of 32.5 years (range, 25-37 years). In 2 of the 7 patients, both class I and class II of panel reactive antibody were high; the remaining 5 patients showed either high in class I or in class II of panel reactive antibody. The mean panel reactive antibody value was 31% for class I and 51% for class II respectively. The donors and the recipients had the same blood type, with low lymphocyte cytotoxicity ranging from 2% to 5%. The human leukocyte antigen (HLA) mismatch numbers were from 2 to 4. All patients received tacrolimus (0.1 mg·kg-1·d-1) and mycophenolate mofetil (750 mg twice per day) orally 3 days prior to surgery. All patients received a single dose of 600 mg rituximab (375 mg/m2) infusion on the day before surgery and polyclonal antibody (antithymocyte globulin) on the day of surgery.Postoperative creatinine, creatinine clearance rate, and occurrence of rejection by pathological biopsy confirmation were monitored.Results No patient had delayed graft function after surgery. Two patients had acute rejection, one on day 7 and the other on day 13 post

  15. Rituximab in the treatment of inflammatory myopathies: a review.

    Science.gov (United States)

    Fasano, Serena; Gordon, Patrick; Hajji, Raouf; Loyo, Esthela; Isenberg, David A

    2017-01-01

    Several uncontrolled studies have encouraged the use of rituximab (RTX) in patients with myositis. Unfortunately, the first placebo-phase trial to assess the efficacy of RTX in refractory myositis did not show a significant difference between the two treatment groups, and doubts have been expressed about its study design. In this review we present an up-to-date overview of the reported experiences of RTX therapy in myositis. A PubMed search was performed to find all the available cases of refractory myositis patients treated with RTX up to July 2015. The following terms were assessed: inflammatory myopathies OR anti-synthetase syndrome OR polymyositis OR dermatomyositis AND RTX. A total of 48 studies were included. We identified 458 patients with myositis treated with RTX. We found a rate of response to RTX of 78.3%. RTX can play a role in the management of patients with myositis, at least in those with positive myositis-specific autoantibodies.

  16. USE OF RITUXIMAB IN AUTOIMMUNE DISEASES: NEW ASPECTS

    Directory of Open Access Journals (Sweden)

    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.

  17. 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.

  18. Future therapies for pemphigus vulgaris: Rituximab and beyond.

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    Huang, Amy; Madan, Raman K; Levitt, Jacob

    2016-04-01

    The conventional treatment for patients with pemphigus vulgaris (PV) centers on global immunosuppression, such as the use of steroids and other immunosuppressive drugs, to decrease titers of antidesmoglein autoantibodies responsible for the acantholytic blisters. Global immunosuppressants, however, cause serious side effects. The emergence of anti-CD20 biologic medications, such as rituximab, as an adjunct to conventional therapy has shifted the focus to targeted destruction of autoimmune B cells. Next-generation biologic medications with improved modes of delivery, pharmacology, and side effect profiles are constantly being developed, adding to the diversity of options for PV treatment. We review promising monoclonal antibodies, including veltuzumab, obinutuzumab (GA-101), ofatumumab, ocaratuzumab (AME-133v), PRO131921, and belimumab.

  19. 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)

  20. 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

  1. Efecto de un anticuerpo monoclonal anti CD20 (Rituximab) en trombocitopenia inmune.

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    Untama, José; Médico, Departamento de Hematología, Hospital Nacional Edgardo Rebagliati Martins – EsSalud. Lima.; Del Carpio, Daniel; Médico, Departamento de Hematología, Hospital Nacional Edgardo Rebagliati Martins – EsSalud. Lima.

    2012-01-01

    Objetivo: Describir la respuesta terapéutica con un anticuerpo monoclonal anti CD20 (Rituximab), en pacientes con Trombocitopenia Inmune (PTI). Material y métodos: Estudio retrospectivo, descriptivo y observacional tipo serie de casos. Se revisaron las historias clínicas de pacientes adultos con PTI que recibieron el anticuerpo monoclonal anti CD20 (Rituximab), desde diciembre 2005 hasta diciembre 2010. Se definió respuesta: conteo plaquetario >30 mil, por lo menos duplicar el conteo plaqu...

  2. Efficacy and safety of rituximab in the treatment of refractory pemfigus vulgaris

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    Aslı Bilgiç Temel

    2015-06-01

    Full Text Available Background and Design: Pemphigus vulgaris (PV is a severe, chronic, potentially life-threatening autoimmune blistering disease that affects the skin and mucous membranes, associated with the loss of cell-cell adhesion and blister formation. Systemic steroids in combination with immunosuppressive agents are the mainstay of therapy in pemphigus. Rituximab is a chimeric monoclonal anti- CD20 antibody, has been tried increasingly for the treatment of PV. Objective: We sought to test the efficacy and safety of rituximab as an adjuvant therapy by retrospective analysis of clinical and immunological data of patients. Method: A retrospective analysis is presented of 13 patients with refractory pemphigus vulgaris who were treated with rituximab at Akdeniz University Hospital, Dermatology and Venereology Department, Bullous Disease Unit. We evaluated clinical and immunological data with last treatments. Results: Patients were treated with one cycle of two biweekly infusions of rituximab at a dose of 1000 mg on days 1 and 15, except one received four doses of 375 mg / m2 intravenously weekly. The mean follow-up time was 18.5 months. All patients had a decrease in antibody titers or antibodies were completely undetected after treatment. Rituximab use resulted in a significant reduction in steroid dosage during follow-up. At the end of the follow-up period, 7 patients achieved complete disease remission without therapy, 1 patient achieved partial disease remission without therapy, 2 patients achieved complete remission on minimal therapy, 1 patient achieved complete remission on therapy, 1 patient achieved partial remission on minimal therapy, and one patient had no follow-up. Rituximab was well tolerated by all patients. Clinical relapse had seen 53.8% by the mean period of 13.8 months. Relapses have been managed with additional infusions of rituximab. Conclusion: Rituximab is beneficial in the management of refractory PV, induces prolonged clinical

  3. 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.

  4. Effective treatment of refractory pulmonary hemorrhage with monoclonal anti-CD20 antibody (rituximab).

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    Pinto, Luis Fernando; Candia, Liliana; Garcia, Patricia; Marín, Juan Ignacio; Pachón, Ines; Espinoza, Luis R; Marquez, Javier

    2009-01-01

    We report a 19-year-old female with systemic lupus erythematosus and lupus nephritis who developed pulmonary hemorrhage (PH) refractory to conventional immunosuppressive treatment. She was initially treated with intravenous methylprednisolone and cyclophosphamide pulses. She required mechanical ventilation due to a lack of responsiveness and her disease was considered refractory to conventional treatment. Rituximab was administered and this was followed by clinical improvement in both PH and nephritis. Rituximab may be a useful therapeutic option for the treatment of refractory PH.

  5. Rituximab is an efficient and safe treatment in adults with steroid-dependent minimal change disease.

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    Munyentwali, Helene; Bouachi, Khedidja; Audard, Vincent; Remy, Philippe; Lang, Philippe; Mojaat, Rachid; Deschênes, Georges; Ronco, Pierre M; Plaisier, Emmanuelle M; Dahan, Karine Y

    2013-03-01

    Development of steroid dependency in patients with nephrotic syndrome may require a long-term multi-drug therapy at risk of drug toxicity and renal failure. Rituximab treatment reduces the steroid dosage and the need for immunosuppressive therapy in pediatric patients. Here we retrospectively analyze the efficacy and safety of rituximab in adult patients with steroid-dependent minimal change disease. To do this, we analyzed the outcome of all adult patients treated with rituximab for steroid-dependent minimal change nephrotic syndrome over a mean follow-up of 29.5 months (range 5.1-82 months). Seventeen patients with steroid-dependent or frequently relapsing minimal change nephrotic syndrome, unresponsive to several immunosuppressive medications, were treated with rituximab. Eleven patients had no relapses after rituximab infusion (mean follow-up 26.7 months, range 5.1-82 months) and nine of them were able to come off all other immunosuppressive drugs and steroids during follow-up. Six patients relapsed at least once after a mean time of 11.9 months (mean follow-up 34.5 months, range 16.9-50.1 months), but their immunosuppressive drug treatment could be stopped or markedly reduced during this time. No adverse events were recorded. Thus, rituximab is efficient and safe in adult patients suffering from severe steroid-dependent minimal change disease. Prospective randomized trials are needed to confirm this study.

  6. Use of Rituximab in Children with Steroid- and Calcineurin-Inhibitor-Dependent Idiopathic Nephrotic Syndrome

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    Ravani, Pietro; Ponticelli, Alessandro; Siciliano, Chiara; Fornoni, Alessia; Magnasco, Alberto; Sica, Felice; Bodria, Monica; Caridi, Gianluca; Wei, Changli; Belingheri, Mirco; Ghio, Luciana; Merscher-Gomez, Sandra; Edefonti, Alberto; Pasini, Andrea; Montini, Giovanni; Murtas, Corrado; Wang, Xiangyu; Muruve, Daniel; Vaglio, Augusto; Martorana, Davide; Pani, Antonello; Scolari, Francesco; Reiser, Jochen; Ghiggeri, Gian Marco

    2013-01-01

    In children with idiopathic nephrotic syndrome rituximab can maintain short-term remission with withdrawal of prednisone and calcineurin-inhibitors. Long-term effects including number of repeated infusions to maintain remission are unknown. We treated with rituximab 46 consecutive children with idiopathic nephrotic syndrome lasting for at least one year (6.3±4.1 years), who were maintained in remission with oral prednisone and calcineurin inhibitors. They received 1–5 rituximab courses during a median follow-up of three years (range 1–5). Oral agents were tapered after each infusion, and completely withdrawn within 45 days. Rituximab was well tolerated. Six-month probabilities of remission were 48% after the first infusion and 37% after subsequent infusions. One- and two-year-remission probabilities were respectively 20% and 10%. Median time intervals between complete oral-agent withdrawal and relapse were 5.6 and 8.5 months respectively following the first and subsequent courses. Time to reconstitution of CD20 cells correlated with the duration of remission, but was not associated with variation in FcyR, CD20 or SMPDL-3B polymorphisms. Podocyte Src phosphorylation was normal. Rituximab can be safely and repeatedly used as prednisone and calcineurin-inhibitor-sparing therapy in a considerable proportion of children with dependent forms of idiopathic nephrotic syndrome. Further research is needed to identify patients who will benefit most from rituximab therapy. PMID:23739238

  7. The Factors That May Predict Response to Rituximab Therapy in Recurrent Focal Segmental Glomerulosclerosis: A Systematic Review

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    Carlos E. Araya

    2011-01-01

    Full Text Available Recurrence of FSGS occurs in 30–40% of allografts. Therapies for recurrence are not well established. We retrieved all published reports depicting kidney transplant recipients with focal segmental glomerulosclerosis (FSGS recurrence, treated with rituximab, to determine factors associated with treatment response. We found 18 reports of 39 transplant recipients who received rituximab. By univariate analysis for two outcomes (no response versus any response, fewer rituximab infusions and normal serum albumin at recurrence were associated with treatment response. For 3 outcomes (no response, partial and complete remission, male gender, fewer rituximab infusions, shorter time to rituximab treatment, and normal serum albumin were associated with remission. Multivariate analysis for both models revealed that normal serum albumin at FSGS recurrence and lower age at transplant were associated with response. Rituximab for recurrence of FSGS may be beneficial for only some patients. A younger age at transplant and normal serum albumin level at recurrence diagnosis may predict response.

  8. Linfoma hepático primario: Evolución favorable con quimioterapia combinada con rituximab Primary hepatic lymphoma: favorable outcome with chemotherapy plus rituximab

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    I. Serrano-Navarro

    2008-11-01

    Full Text Available Comunicamos el caso de una paciente con un linfoma hepático primario tratado con éxito con quimioterapia combinada con rituximab. Utilizando los "encabezamientos estándar para búsquedas bibliográficas informatizadas" (Medical Subject Heading revisamos los casos publicados hasta la fecha de esta infrecuente entidad.This article describes the case of a patient with a non-Hodgkin primary hepatic lymphoma who was successfully treated with chemotherapy combined with rituximab. Using the Medical Subject Headings the published reports of this rare entity were reviewed.

  9. Rituximab in the treatment of B-cell non-Hodgkin lymphoma, focus on outcomes and comparative effectiveness

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    Firas Badin

    2010-04-01

    Full Text Available Firas Badin, John HayslipUniversity of Kentucky, Markey Cancer Center, Lexington, KY, USAAbstract: Rituximab is an important and well established component in the treatment of many patients with B-cell non-Hodgkin lymphoma. In this paper we review recent clinical trials investigating the addition of rituximab to standard chemotherapy regimens for treatment of patients with diffuse large B cell lymphoma and follicular lymphoma. This report focuses upon treatment efficacy, quality of life, and safety of rituximab or rituximab-containing regimens. More uniquely, we review economic aspects of lymphoma treatments, including the cost of standard chemotherapy regimens with or without rituximab, cost effectiveness of rituximab in both induction and maintenance treatment, and lymphoma’s impacts on patient’s productivity and their caregivers. We conclude that adding rituximab to standard chemotherapy treatment for patients with B-cell non-Hodgkin lymphoma is safe and cost-effective in numerous settings during both induction and maintenance therapies. Despite extensive review of the literature, many important questions have yet to be answered in the rituximab era and these represent important directions for future study.Keywords: rituximab, lymphoma, cost effectiveness, transplant, safety

  10. Con: Should all patients with anti-neutrophil cytoplasmic antibody-associated vasculitis be primarily treated with rituximab?

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    Kronbichler, Andreas; Jayne, David R W

    2015-07-01

    Rituximab has enriched our armamentarium in the treatment of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis. Two randomised controlled trials have shown that rituximab is non-inferior compared with cyclophosphamide followed by azathioprine for the induction of remission. The newly diagnosed patients in the Rituximab in ANCA-Associated Vasculitis (RAVE) and Rituximab Versus Cyclophosphamide in ANCA-Associated Vasculitis (RITUXVAS) trials had a numerically higher response rate in the cyclophosphamide/azathioprine arm, and the number of such patients treated with rituximab numbered cases and late-onset neutropaenia are complications not seen with cyclophosphamide. Over the longer term it is unclear what relapse prevention strategy should be employed after rituximab, and there was a trend to a higher relapse risk after rituximab in the RITUXVAS trial at 2 years. Further health economic studies are required to understand all the costs associated with rituximab. In the context of concomitant underlying infectious complications, in terms of fertility concerns, especially in young patients, and when malignancy is underlying we would recommend the use of rituximab as first-line therapy.

  11. Rituximab efficiently depletes B cells in lung tumors and normal lung tissue [version 1; referees: 2 approved

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    Albane Joly-Battaglini

    2016-01-01

    Full Text Available Rituximab is a monoclonal antibody that targets the CD20 B-cell-specific antigen and is widely used as therapy for B-cell lymphoma. Since rituximab depletes both malignant and normal B cells, it is increasingly being used to treat various conditions in which normal B cells have a pathogenic role, such as rheumatoid arthritis and multiple sclerosis. It is well-established that rituximab efficiently eliminates B cells in blood, lymph nodes, and spleen. In contrast, the effect of rituximab in non-lymphoid tissues remains poorly documented and is debated. Here, we report a rheumatoid arthritis patient who was treated with rituximab before receiving thoracic surgery for non-small cell lung cancer. Using flow cytometry and immunohistochemistry, we show that rituximab efficiently depleted CD20-positive B cells in a primary lung tumor, in lung-associated lymph nodes, and in normal lung tissue. We conclude that rituximab may be very efficient at depleting normal B cells in the lungs. This property of rituximab may potentially be exploited for the treatment of conditions in which pathogenic B cells reside in the lungs. On the other hand, the clearance of lung B cells may provide an explanation for the rare cases of severe non-infectious pulmonary toxicity of rituximab.

  12. The Result of Multiple I-131 Treatments on the Effective Half-Life of Retained Radioactivity in Patients Ablated for Differentiated Thyroid Cancer: Possible Evidence for Thyroid Remnant Function Impairment.

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    Okkalides, Demetrios

    2016-03-01

    The ablation of differentiated thyroid cancer by ingested I-131 depends on the activity absorbed by the remnant. This depends on the function of the thyroid cells and on the rate that radioactivity is excreted from the blood. The reduction of radioiodine is described by the effective half-life (EHL), which is the time taken to half the retained radioactivity. If the tumor recurs, more treatments are prescribed, often with escalating activities. Patients may receive several treatments during the evolution of the disease, and the total radioactivity administered (TRA) is the sum of all such activities. The patients' archived information permitted the calculation of EHL and TRA. The patient cohort processed here comprised 274 females and 101 males treated during 1997 to 2015. The TRA to the patients ranged between 1.1 and 129.5 GBq (average = 7.93 ± 9.9 GBq) and the EHL varied between 5.06 and 43.87 hours (average = 14.13 ± 5.7 hours). The data were processed as follows: (a) the EHL corresponding to the last treatment of each patient was plotted against TRA to patients who were treated once and to those treated several times for comparison and (b) using a small subgroup of 16 patients who were treated at least 5 times, the EHL and TRA corresponding to each treatment of each patient were plotted. A function of the form y = p-k·ln(x) was fitted on the data in all graphs and k was calculated. For patients treated once, EHL was independent of TRA. A decrease was seen in (a) multitreated patients, with the gradient (k) ranging between -0.541 and -13.880 and (b) 13 out of 16 patients, with the gradient (k) ranging between -5.55 and -31.17, both indicating an impairment of the remnant function, perhaps identified as "stunning." Since this is not avoidable, the uptake may be boosted by splitting the prescribed activity into low radioactivity fractions, which will also reduce patient hospitalization.

  13. Safety and efficacy of combined cyclophosphamide and rituximab treatment in recalcitrant childhood lupus.

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    Ale'ed, Ashwaq; Alsonbul, Abdullah; Al-Mayouf, Sulaiman M

    2014-04-01

    To report the safety and efficacy of combined cyclophosphamide and rituximab treatment in Saudi children with systemic lupus erythematosus (SLE). Medical records of all children with SLE treated with cyclophosphamide and rituximab between June 2007 and June 2012 at King Faisal Specialist Hospital and Research Center, Riyadh, were reviewed for demographic characteristics, age at diagnosis, concomitant treatments, indication of using rituximab and adverse events during the treatment period. Clinical and serologic response parameters included SLE Disease Activity Index (SLEDAI), complement, anti-ds DNA antibody and ANA levels, and mean daily corticosteroid dose assessed 3 months before combined cyclophosphamide and rituximab infusion course and at 6-month interval afterward. Sixteen patients (13 girls) with refractory SLE treated with cyclophosphamide and rituximab were included. The mean age at onset of SLE was 7.8 + 3.3 years, while the mean age at diagnosis was 8.1 + 3.4 years; the mean disease duration was 4.7 + 3.2 years. All patients were treated with corticosteroid and immunosuppressive drugs. Nephritis (8 patients) was the most frequent indication; other indications included refractory arthritis, thrombocytopenia, severe mucocutaneous lesions and central nervous system involvement. All patients received 2 doses, but 4 required 4-8 extra doses. All patients showed improvement in response parameters. There was significant reduction in SLEDAI (P < 0.0002) and corticosteroid dose (P < 0.005). A total of 4 adverse events were notified; 2 developed infusion-related reactions. One patient had severe soft tissue fungal infection, and other patient had pancreatitis. Our data showed beneficial therapeutic and steroid-sparing effects of rituximab as adjunctive treatment for children with refractory SLE including both renal and extrarenal manifestations. Although rituximab was well tolerated by the majority of patients, it may associated with various adverse events.

  14. A comprehensive analysis of treatment outcomes in patients with pemphigus vulgaris treated with rituximab.

    Science.gov (United States)

    Ahmed, A Razzaque; Shetty, Shawn

    2015-04-01

    Approximately 500 treatment recalcitrant pemphigus vulgaris patients have been treated with rituximab. They were treated according to the lymphoma protocol (N=224) or rheumatoid arthritis protocol (RAP) (N=209) patients. Others were treated with modifications or combinations of the two. The mean duration of follow-up with the lymphoma protocol was 28.9months and 21.9 in the rheumatoid arthritis protocol. The majority of the patients received corticosteroids and immunosuppressive therapy before, during, and after rituximab therapy. A clinical remission on therapy was observed in 90%-95% of patients within less than six weeks. A complete resolution occurred within three to four months. A small percentage of patients were able to stay in clinical remission without the need for additional systemic therapy. The incidence of relapse was at least 50%. The number of patients who required additional rituximab was 60% to 90%. A majority of patients in clinical remission post-rituximab therapy, were still on CS and ISA, albeit at lower doses. Serious adverse events were reported in a mean of five patients (range 2-9), the most important was infection and frequently resulting in septicemia. The mortality rate related to rituximab was a mean of 2 patients (range 1-3). Hence, the preliminary conclusions that can be drawn are that rituximab is an excellent agent to induce early remission. The protocols that were used were not ideal for producing a prolonged and sustained remission without additional therapy. The advantages and specificity of targeting B-cells demonstrate that rituximab is one of the best biological agents, currently available for treating recalcitrant pemphigus. Its further use is encouraged. Future research needs to focus on modifying, improving and possibly adding additional agents, so that prolonged and sustained remissions can be obtained by its use.

  15. Anti CD20 (Rituximab therapy in refractory pediatric rheumatic diseases

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    Joel Reis

    2016-01-01

    Full Text Available Objectives: We aim to report the efficacy and safety of rituximab (RTX in patients diagnosed with juvenile systemic lupus erythematosus (JSLE or juvenile idiopathic arthritis (JIA refractory to conventional treatment. Methods: A retrospective review was made of all medical records of patients with JSLE or JIA treated with RTX between January 2009 and January 2015 in the Pediatric Rheumatology Unit of a central hospital. Results: Five patients, 4 with JSLE and 1 with extended oligoarticular JIA, received 10 cycles of RTX (23 infusions. The scheme of RTX frequently used was 750 mg/m2 two weeks apart. The median follow-up time after receiving the first cycle of RTX was 24 months (12 – 70. The four patients with JSLE were female (three caucasian and one black. The patient with JIA was a caucasian male. The median age at diagnosis was 10 years (16 months – 17years. The median evolution time until receiving RTX was 6 years (5 months – 15 years. Refractory class IV lupus nephritis was the most common indication for receiving RTX. Previous treatment to RTX included nonsteroidal anti-inflammatory drugs, disease-modifying anti-rheumatic drugs, immunosuppressive drugs and corticosteroids in all patients and anti-TNFα (etanercept in the patient with JIA. It was possible to reduce the mean oral corticosteroid dose after RTX, ranging from 23 mg/day (20-25mg/day before RTX to 11 mg/day (0–20 mg/day at the last evaluation. Disease activity before RTX and at last evaluation also improved. The SLEDAI score, for JSLE, decreased from a median of 15, 5 (11 – 18 to 3 (0 – 6, and the JADAS-27 score, for JIA, also diminished from 40.4 to 3.5. Adverse events occurred in 2 patients, including delayed second dose after the diagnosis of cryptococcosis and respiratory tract infection with concomitant hypogammaglobulinemia needing of immunoglobulin replacement and antibiotic therapy. Conclusions: Rituximab might have a role in the treatment of JSLE and JIA

  16. Rituximab maintenance therapy for patients with diffuse large B-cell lymphoma: A meta-analysis

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    Li, Juan

    2017-01-01

    Purpose The addition of rituximab to standard chemotherapy has significantly improved survival in patients with lymphoma. Recently, maintenance therapy with rituximab has been shown to prevent relapse and provide survival benefits for patients with follicular or mantle cell lymphoma. However, the effects of rituximab in patients with diffuse large B-cell lymphoma (DLBCL) remain unclear. Two new studies involving rituximab in the treatment of DLBCL were performed this past year. We performed a meta analysis to evaluate the effects of rituximab maintenance treatment of patients with DLBCL. Methods Several databases (PubMed, MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials) databases were reviewed for relevant randomized controlled trials published prior to May, 2016. Two reviewers assessed the quality of the included studies and extracted data independently. The hazard ratios (HRs) for time-to-event data and relative risks (RRs) for the other data were pooled and estimated. Results Totally 5 studies including 1740 patients were eligible for the meta-analysis. Compared to the observation group, patients who received rituximab maintenance therapy had significantly improved event-free survival (EFS) (HR = 0.80, 95% CI: 0.65–0.98) and progression-free survival (PFS) (HR = 0.72, 95% CI: 0.54–0.94). However, there was no statistically significant difference in overall survival (OS) (HR = 0.66, 95% CI: 0.27–1.29). A subgroup analysis suggested that male patients may benefit from rituximab maintenance therapy with a better EFS (HR = 0.53, 95% CI: 0.34–0.82-), while this advantage was not observed in female patients (HR = 0.99, 95% CI: 0.64–1.52). Conclusions Rituximab maintenance may provide survival benefits beyond that afforded by first- and second-line chemotherapy alone, especially in male patients. However, maintenance rituximab treatment may cause more adverse events. It is recommended that both survival benefits and adverse events should

  17. Remission Achieved in Refractory Advanced Takayasu Arteritis Using Rituximab

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    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.

  18. Practical considerations on the use of rituximab in autoimmune neurological disorders

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    Kosmidis, Mixalis L.; Dalakas, Marinos C.

    2010-01-01

    Rituximab (Mabthera, Rituxan) is a chimeric human/murine monoclonal antibody against CD-20 surface antigen expressed on B-cells. Rituximab, by causing B-cell depletion, appears to be effective in several autoimmune disorders; it has been approved for rheumatoid arthritis and is a promising new agent in the treatment of several autoimmune neurological disorders. A controlled study in patients with relapsing remitting multiple sclerosis has shown that rituximab significantly reduces the number of new MRI lesions and improves clinical outcome; it also showed some promise in a subset of patients with primary progressive MS. The drug is also effective in a number of patients with Devic’s disease, myasthenia gravis, autoimmune neuropathies, and inflammatory myopathies. The apparent effectiveness of rituximab has moved B-cells into the center stage of clinical and laboratory investigation of autoimmune neurological disorders. We review the evidence-based effectiveness of rituximab in neurological disorders based on controlled trials and anecdotal reports, including our own experience, and address the immunobiology of B-cells in autoimmune central nervous system (CNS) and peripheral nervous system (PNS) disorders. In addition, we provide practical guidelines on how best to use this drug in clinical practice and highlight its potential toxicity. PMID:21179602

  19. Practical considerations on the use of rituximab in autoimmune neurological disorders.

    Science.gov (United States)

    Kosmidis, Mixalis L; Dalakas, Marinos C

    2010-03-01

    Rituximab (Mabthera, Rituxan) is a chimeric human/murine monoclonal antibody against CD-20 surface antigen expressed on B-cells. Rituximab, by causing B-cell depletion, appears to be effective in several autoimmune disorders; it has been approved for rheumatoid arthritis and is a promising new agent in the treatment of several autoimmune neurological disorders. A controlled study in patients with relapsing remitting multiple sclerosis has shown that rituximab significantly reduces the number of new MRI lesions and improves clinical outcome; it also showed some promise in a subset of patients with primary progressive MS. The drug is also effective in a number of patients with Devic's disease, myasthenia gravis, autoimmune neuropathies, and inflammatory myopathies. The apparent effectiveness of rituximab has moved B-cells into the center stage of clinical and laboratory investigation of autoimmune neurological disorders. We review the evidence-based effectiveness of rituximab in neurological disorders based on controlled trials and anecdotal reports, including our own experience, and address the immunobiology of B-cells in autoimmune central nervous system (CNS) and peripheral nervous system (PNS) disorders. In addition, we provide practical guidelines on how best to use this drug in clinical practice and highlight its potential toxicity.

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

    Science.gov (United States)

    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.

  1. Rituximab as Single Agent in Primary MALT Lymphoma of the Ocular Adnexa

    Directory of Open Access Journals (Sweden)

    Ombretta Annibali

    2015-01-01

    Full Text Available Ocular Adnexal Lymphomas are the first cause of primary ocular malignancies, and among them the most common are MALT Ocular Adnexal Lymphomas. Recently systemic immunotherapy with anti-CD20 monoclonal antibody has been investigated as first-line treatment; however, the optimal management for MALT Ocular Adnexal Lymphomas is still unknown. The present study evaluated retrospectively the outcome of seven consecutive patients with primary MALT Ocular Adnexal Lymphomas, of whom six were treated with single agent Rituximab. All patients received 6 cycles of Rituximab 375 mg/mq every 3 weeks intravenously. The overall response rate was 100%; four patients (67% achieved a Complete Remission, and two (33% achieved a partial response. In four patients an additional Rituximab maintenance every 2-3 months was given for two years. After a median follow-up of 29 months (range 8–34, no recurrences were observed, without of therapy- or disease-related severe adverse events. None of the patients needed additional radiotherapy or other treatments. Rituximab as a single agent is highly effective and tolerable in first-line treatment of primary MALT Ocular adnexal Lymphomas. Furthermore, durable responses are achievable with the same-agent maintenance. Rituximab can be considered the agent of choice in the management of an indolent disease in whom the “quality of life” matter is of primary importance.

  2. Rituximab as Single Agent in Primary MALT Lymphoma of the Ocular Adnexa.

    Science.gov (United States)

    Annibali, Ombretta; Chiodi, Francesca; Sarlo, Chiara; Cortes, Magdalena; Quaranta-Leoni, Francesco M; Quattrocchi, Carlo; Bianchi, Antonella; Bonini, Stefano; Avvisati, Giuseppe

    2015-01-01

    Ocular Adnexal Lymphomas are the first cause of primary ocular malignancies, and among them the most common are MALT Ocular Adnexal Lymphomas. Recently systemic immunotherapy with anti-CD20 monoclonal antibody has been investigated as first-line treatment; however, the optimal management for MALT Ocular Adnexal Lymphomas is still unknown. The present study evaluated retrospectively the outcome of seven consecutive patients with primary MALT Ocular Adnexal Lymphomas, of whom six were treated with single agent Rituximab. All patients received 6 cycles of Rituximab 375 mg/mq every 3 weeks intravenously. The overall response rate was 100%; four patients (67%) achieved a Complete Remission, and two (33%) achieved a partial response. In four patients an additional Rituximab maintenance every 2-3 months was given for two years. After a median follow-up of 29 months (range 8-34), no recurrences were observed, without of therapy- or disease-related severe adverse events. None of the patients needed additional radiotherapy or other treatments. Rituximab as a single agent is highly effective and tolerable in first-line treatment of primary MALT Ocular adnexal Lymphomas. Furthermore, durable responses are achievable with the same-agent maintenance. Rituximab can be considered the agent of choice in the management of an indolent disease in whom the "quality of life" matter is of primary importance.

  3. Place in therapy of rituximab in the treatment of granulomatosis with polyangiitis and microscopic polyangiitis.

    Science.gov (United States)

    Shah, Shivani; Geetha, Duvuru

    2015-01-01

    Granulomatosis with polyangiitis and microscopic polyangiitis are small vessel vasculitides characterized by circulating antineutrophil circulating antibodies. Standard treatment for active severe disease has consisted of cyclophosphamide with glucocorticoids with or without plasmapheresis, which achieves approximately 75% sustained remission, but carries significant adverse effects such as malignancy, infertility, leukopenia, and infections. The role of B cells in the pathogenesis of anti-neutrophil circulating antibodies-associated vasculitis has been established, and as such, rituximab, a monoclonal anti-CD20 antibody, has been studied in treatment of active granulomatosis with polyangiitis and microscopic polyangiitis (induction) and in maintaining remission. Rituximab has been shown to be effective in inducing remission in several retrospective studies in patients with refractory disease or cyclophosphamide intolerance. The RAVE and RITUXVAS trials demonstrated rituximab is a noninferior alternative to standard cyclophosphamide-based therapy; however, its role in elderly patients and patients with severe renal disease warrants further investigation. Rituximab has been compared with azathioprine for maintaining remission in the MAINRITSAN trial and may be more efficacious in maintaining remission in patients treated with cyclophosphamide induction. Rituximab is not without risks and carries a similar adverse event risk rate as cyclophosphamide in randomized control trials. However, its use can be considered over cyclophosphamide in patients who have relapsing or refractory disease or in young patients seeking to preserve fertility.

  4. Clinical response, pharmacokinetics, development of human anti-chimaeric antibodies, and synovial tissue response to rituximab treatment in patients with rheumatoid arthritis

    NARCIS (Netherlands)

    R.M. Thurlings; O. Teng; K. Vos; D.M. Gerlag; L. Aarden; S.O. Stapel; J.M. van Laar; P.P. Tak; G.J. Wolbink

    2010-01-01

    Objectives: To analyse whether persistence of synovial B lineage cells and lack of clinical response to rituximab treatment in patients with rheumatoid arthritis (RA) are associated with low rituximab serum levels and anti-rituximab antibody (ARA) formation. Methods: Fifty-eight patients with RA wer

  5. Superior activity of fusion protein scFvRit : sFasL over cotreatment with rituximab and Fas agonists

    NARCIS (Netherlands)

    Bremer, Edwin; ten Cate, Bram; Samplonius, Douwe F.; Mueller, Nicole; Wajant, Harald; Stel, Aja J.; Chamuleau, Martine; de Loosdrecht, Arjan A. van; Stieglmaier, Julia; Fey, Georg H.; Helfrich, Wijnand

    2008-01-01

    The clinical efficacy of the CD20-specific chimeric monoclonal antibody rituximab is significantly hampered by intrinsic or acquired resistance to therapy. Rituximab activates antibody-dependent cellular cytotoxicity/complement-dependent cytotoxicity-dependent lysis but also induces apoptosis by cro

  6. Inhibition of joint damage and improved clinical outcomes with rituximab plus methotrexate in early active rheumatoid arthritis: the IMAGE trial

    NARCIS (Netherlands)

    P.P. Tak; W.F. Rigby; A. Rubbert-Roth; C.G. Peterfy; R.F. van Vollenhoven; W. Stohl; E. Hessey; A. Chen; H. Tyrrell; T.M. Shaw

    2011-01-01

    Objectives Rituximab is an effective treatment in patients with established rheumatoid arthritis (RA). The objective of the IMAGE study was to determine the efficacy of rituximab in the prevention of joint damage and its safety in combination with methotrexate (MTX) in patients initiating treatment

  7. Methodology to administer therapeutic dose of I-131; Metodologia para administrar dosis terapeutica de I-131

    Energy Technology Data Exchange (ETDEWEB)

    Basteris M, J.; Gomez D, R. [Universidad Autonoma de Yucatan, Facultad de Medicina, Merida, Yucatan (Mexico)

    2007-07-01

    The present work suggests the use of measures guided to eliminate the resulting chronic sialoadenitis of the treatment of the thyroid cancer with Iodine-131, as well as the use of citric fruits to stimulate the salivation, the post-dose administration of liquids to accelerate the gastric emptying avoiding the secondary effects as the vomit is included. (Author)

  8. Rituximab Not Effective for Hearing Loss in Cogan’s Syndrome

    Directory of Open Access Journals (Sweden)

    Daniel R. Bunker

    2016-01-01

    Full Text Available Importance. Rituximab was not effective in ameliorating the hearing loss in a patient with atypical Cogan’s syndrome. Observations. We report the case of a patient who developed acute bilateral uveitis and sensorineural hearing loss. A diagnosis of atypical Cogan’s syndrome was made. The patient’s hearing loss did not improve despite high dose steroids and azathioprine. Rituximab was administered given a recent report of its efficacy in a patient with refractory disease; however, our patient’s hearing loss did not improve. Conclusion. Hearing loss in Cogan’s syndrome is difficult to treat. Though rituximab was ineffective in our case, earlier administration in the disease course could be effective for future patients.

  9. Rituximab: an emerging treatment for recurrent diffuse alveolar hemorrhage in systemic lupus erythematosus.

    Science.gov (United States)

    Tse, J R; Schwab, K E; McMahon, M; Simon, W

    2015-06-01

    Diffuse alveolar hemorrhage (DAH) is a rare manifestation of systemic lupus erythematosus (SLE) and is associated with high mortality rates. Treatment typically consists of aggressive immunosuppression with pulse-dose steroids, cyclophosphamide, and plasma exchange therapy. Mortality rates remain high despite use of multiple medical therapies. We present a case of recurrent DAH in a 52-year-old female with SLE after a deceased donor renal transplant who was successfully treated with rituximab. Our report highlights the pathophysiologic importance of B-cell-mediated immunosuppression in SLE-associated DAH and suggests that rituximab may represent a viable alternative to cyclophosphamide in the treatment of this disease. We also review eight other reported cases of rituximab use in SLE-associated DAH.

  10. The Efficacy and Safety of Rituximab in a Patient with Rheumatoid Spondylitis

    Directory of Open Access Journals (Sweden)

    Şenol Kobak

    2013-01-01

    Full Text Available Rheumatoid arthritis (RA is considered as a connective tissue disease while ankylosing spondylitis (AS is a prototype of spondyloarthritis. These diseases are seen concomitantly only very rarely. Also, rituximab has proven efficacy in the treatment of RA while its role in the treatment of AS is unclear. In this presentation, the concomitant presence of RA and AS in a 43-year-old male patient as well as the efficacy and safety of rituximab is discussed. Rituximab was given due to lack of response to treatment with anti-TNF-alpha. Evaluations made at the 6th and 12th months of treatment showed complete response for RA and partial response for AS.

  11. Rituximab in Adult –Onset Still’s Disease: Case Report

    Directory of Open Access Journals (Sweden)

    G Mehrpoor

    2009-01-01

    Full Text Available Summary: Adult-onset Still’s disease (AOSD is a rare systemic inflammatory disorder of unknown etiology. It is characterized by high grade fever, skin rash, arthritis, leukocytosis, increased ESR, CRP and liver enzyme levels and high levels of ferritin. The treatment of AOSD includes NSAIDs, steroids, and disease-modifying antirheumatic drugs (DMARDs. Recently biologic agents have been used for treatment of some rheumatologic disorders. Rituximab(MabThera, an anti-CD20 monoclonal antibody is one of the biologic agents which is used by only a few researchers for treatment of refractory AOSD. Herein, we describe a 23 year old woman, who was treated with Rituximab ,three years after diagnosis of AOSD .She did not respond to Metotroxate and Cellcept .After administration of Rituximab, clinical and laboratory remission was achieved .

  12. Detecting CD20-Rituximab specific interactions on lymphoma cells using atomic force microscopy

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    Elucidating the underlying mechanisms of cell physiology is currently an important research topic in life sciences. Atomic force microscopy methods can be used to investigate these molecular mechanisms. In this study, single-molecule force spectroscopy was used to explore the specific recognition between the CD20 antigen and anti-CD20 antibody Rituximab on B lymphoma cells under near-physiological conditions. The CD20-Rituximab specific binding force was measured through tip functionalization. Distribution of CD20 on the B lymphoma cells was visualized three-dimensionally. In addition, the relationship between the intramolecular force and the molecular extension of the CD20-Rituximab complex was analyzed under an external force. These results facilitate further investigation of the mechanism of Rituximab’s anti-cancer effect.

  13. Place in therapy of rituximab in the treatment of granulomatosis with polyangiitis and microscopic polyangiitis

    Directory of Open Access Journals (Sweden)

    Shah S

    2015-08-01

    Full Text Available Shivani Shah, Duvuru Geetha Department of Medicine, Division of Nephrology, Johns Hopkins University School of Medicine, Baltimore, MD, USA Abstract: Granulomatosis with polyangiitis and microscopic polyangiitis are small vessel vasculitides characterized by circulating antineutrophil circulating antibodies. Standard treatment for active severe disease has consisted of cyclophosphamide with glucocorticoids with or without plasmapheresis, which achieves approximately 75% sustained remission, but carries significant adverse effects such as malignancy, infertility, leukopenia, and infections. The role of B cells in the pathogenesis of anti-neutrophil circulating antibodies-associated vasculitis has been established, and as such, rituximab, a monoclonal anti-CD20 antibody, has been studied in treatment of active granulomatosis with polyangiitis and microscopic polyangiitis (induction and in maintaining remission. Rituximab has been shown to be effective in inducing remission in several retrospective studies in patients with refractory disease or cyclophosphamide intolerance. The RAVE and RITUXVAS trials demonstrated rituximab is a noninferior alternative to standard cyclophosphamide-based therapy; however, its role in elderly patients and patients with severe renal disease warrants further investigation. Rituximab has been compared with azathioprine for maintaining remission in the MAINRITSAN trial and may be more efficacious in maintaining remission in patients treated with cyclophosphamide induction. Rituximab is not without risks and carries a similar adverse event risk rate as cyclophosphamide in randomized control trials. However, its use can be considered over cyclophosphamide in patients who have relapsing or refractory disease or in young patients seeking to preserve fertility. Keywords: rituximab, ANCA-associated vasculitis, GPA, MPA, induction therapy, maintenance therapy

  14. 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.

  15. Preliminary analysis of mortality associated with rituximab use in autoimmune diseases.

    Science.gov (United States)

    Shetty, Shawn; Ahmed, A R

    2013-12-01

    Normal antibodies and pathogenic autoantibodies are produced by B-cells and plasma cells. Rituximab is a chimeric monoclonal antibody that targets the CD20 molecule on cells that express them on their surface and kills them. Rituximab has been increasingly used to treat several autoimmune diseases. Studies on fatal outcomes associated with rituximab therapy are lacking. A comprehensive and detailed analysis in which the multiple factors that could contribute to a fatal outcome in all the autoimmune diseases in which rituximab has been used would be cumbersome, lack uniformity and would prove difficult in making certain definitive conclusions and comparisons, but more importantly it would not allow to provide specific precautions and recommendations to prevent mortality. Hence, autoimmune mucocutaneous blistering diseases (AMBD) were used as model to study fatal outcomes in patients treated with rituximab between 2000 and 2013, using uniform 13 criteria. Fatal outcomes were found in 14 patients with autoimmune blistering diseases out of 134 patients (10.4%). Patients died due to infections (75%), gastrointestinal (17%) and cardiac events (8%). Causes of death were reported in 101 patients with other autoimmune diseases out of 4320 with a mortality rate of 2.4%. Among them, 44 patients (43.6%) died from infections. A statistical analysis of the data demonstrated that a statistically significant higher mortality rate was observed in patients with AMBD compared to patients with other autoimmune diseases. Similarly, a statistically significant higher rate of death due to infections was reported in patients with AMBD compared to patients with other autoimmune diseases. Use of systemic corticosteroids and immunosuppressive agents as concomitant therapy with rituximab enhanced immunosuppression. In many patients, B-cells were depleted for prolonged periods, even after clinical recovery was observed. Although its main action is depletion of B-cells, rituximab has a

  16. Treatment of immune thrombocytopenia after allogeneic cord blood stem cell transplantation with rituximab: a case report

    Institute of Scientific and Technical Information of China (English)

    Mengxing Li; Jishi Wang; Yan Zhang; Zhiqiang Sun; Yanju Li; Xiaoli Zhou

    2013-01-01

    Immune thrombocytopenia (ITP) is a chronic disease resulting from increased platelet destruction and impaired platelet production. Secondary ITP can be a manifestation of chronic graft-versus-host disease (GVHD) and represent a lymphoproliferative disorder. A boy with chronic graft-versus-host disease after cord blood stem cell transplantation who had severe refractory immune-mediated thrombocytopenia received infusion of rituximab weekly, 375 mg/m2, for 4 weeks. Platelets count of the patient was recovered, and rituximab was well tolerated with no severe toxicity observed during treatment.

  17. 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.

  18. The role of rituximab in adults with warm antibody autoimmune hemolytic anemia.

    Science.gov (United States)

    Dierickx, Daan; Kentos, Alain; Delannoy, André

    2015-05-21

    Warm antibody hemolytic anemia is the most common form of autoimmune hemolytic anemia. When therapy is needed, corticosteroids remain the cornerstone of initial treatment but are able to cure only a minority of patients (hemolytic anemia in adults, although no prospective study convincingly supports this attitude. A recent randomized study strongly suggests that in first-line treatment, rituximab combined with steroids is superior to monotherapy with steroids. If this finding is confirmed, rituximab will emerge as a major component of the management of warm antibody hemolytic anemia not only after relapse but as soon as treatment is needed.

  19. Comparative assessment of clinical response in patients with rheumatoid arthritis between PF‐05280586, a proposed rituximab biosimilar, and rituximab

    Science.gov (United States)

    Williams, Jason H.; Hutmacher, Matthew M.; Zierhut, Matthew L.; Becker, Jean‐Claude; Gumbiner, Barry; Spencer‐Green, George; Melia, Lisa A.; Liao, Kai‐Hsin; Suster, Matthew; Li, Ruifeng; Meng, Xu

    2016-01-01

    Aims To evaluate potential differences between PF‐05280586 and rituximab sourced from the European Union (rituximab‐EU) and USA (rituximab‐US) in clinical response (Disease Activity Score in 28 Joints [DAS28] and American College of Rheumatology [ACR] criteria), as part of the overall biosimilarity assessment of PF‐05280586. Methods A randomised, double‐blind, pharmacokinetic similarity trial was conducted in patients with active rheumatoid arthritis refractory to anti‐tumour necrosis factor therapy on a background of methotrexate. Patients were treated with 1000 mg of PF‐05280586, rituximab‐EU or rituximab‐US on days 1 and 15 and followed over 24 weeks for pharmacokinetic, clinical response and safety assessments. Key secondary end points were the areas under effect curves for DAS28 and ACR responses. Mean differences in areas under effect curves were compared against respective reference ranges established by observed rituximab‐EU and rituximab‐US responses using longitudinal nonlinear mixed effects models. Results The analysis included 214 patients. Demographics were similar across groups with exceptions in some baseline disease characteristics. Baseline imbalances and group‐to‐group variation were accounted for by covariate effects in each model. Predictions from the DAS28 and ACR models tracked the central tendency and distribution of observations well. No point estimates of mean differences were outside the reference range for DAS28 or ACR scores. The probabilities that the predicted differences between PF‐05280586 vs. rituximab‐EU or rituximab‐US lie outside the reference ranges were low. Conclusions No clinically meaningful differences were detected in DAS28 or ACR response between PF‐05280586 and rituximab‐EU or rituximab‐US as the differences were within the pre‐specified reference ranges. TRIAL REGISTRATION Number: NCT01526057. PMID:27530379

  20. Efficacy and safety of rituximab therapy for systemic lupus erythematosus: a systematic review and meta-analysis

    Institute of Scientific and Technical Information of China (English)

    Lan LAN; Fei HAN; Jiang-hua CHEN

    2012-01-01

    Objective:To review the efficacy and safety of rituximab therapy for systemic lupus erythematosus (SLE).Methods:We searched for randomized controlled trails and observational studies that evaluated the effect of rituximab based on the systemic lupus erythematosus disease activity index (SLEDAI),British Isles lupus assessment group index (BILAG),urine protein levels,and the prednisolone dose,and had adequate data to calculate the mean,standard deviation (SD),and 95% confidence intervals,and to systematically review and meta-analyze observational studies with fixed effects model or random effects model.Results:We included 2 randomized controlled studies and 19observational clinical studies.We summarized the data from the 19 observational studies,analyzed the heterogeneity of the literature,and then used fixed effect model or random effect model for statistical analysis.The SLEDAI,BILAG,and urine protein levels and the prednisolone dosage were decreased after rituximab treatment,and the decreases in the BILAG,urine protein levels,and the prednisolone dose were found to be significant (P<0.05),when compared with baseline level.Rituximab's adverse effects generally could be controlled with an effective dosing regimen.Conclusions:Although there are still controversies about rituximab's treatment on SLE,but our study had showed that rituximab had favorable effects on refractory lupus.The long-term efficacy and safety of rituximab require further study.

  1. A pioneer experience in Malaysia on In-house Radio-labelling of (131)I-rituximab in the treatment of Non-Hodgkin's Lymphoma and a case report of high dose (131)I-rituximab-BEAM conditioning autologous transplant.

    Science.gov (United States)

    Kuan, Jew Win; Law, Chiong Soon; Wong, Xiang Qi; Ko, Ching Tiong; Awang, Zool Hilmi; Chew, Lee Ping; Chang, Kian Meng

    2016-10-01

    Radioimmunotherapy is an established treatment modality in Non-Hodgkin's lymphoma. The only two commercially available radioimmunotherapies - (90)Y-ibritumomab tiuxetan is expensive and (131)I-tositumomab has been discontinued from commercial production. In resource limited environment, self-labelling (131)I-rituximab might be the only viable practical option. We reported our pioneer experience in Malaysia on self-labelling (131)I-rituximab, substituting autologous haematopoietic stem cell transplantation (HSCT) and a patient, the first reported case, received high dose (131)I-rituximab (6000MBq/163mCi) combined with BEAM conditioning for autologous HSCT.

  2. Rituximab purging and/or maintenance in patients undergoing autologous transplantation for relapsed follicular lymphoma

    DEFF Research Database (Denmark)

    Pettengell, Ruth; Schmitz, Norbert; Gisselbrecht, Christian

    2013-01-01

    The objective of this randomized trial was to assess the efficacy and safety of rituximab as in vivo purging before transplantation and as maintenance treatment immediately after high-dose chemotherapy and autologous stem-cell transplantation (HDC-ASCT) in patients with relapsed follicular lymphoma...

  3. 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

    Treatment of Graves' disease (GD) with the B-lymphocyte depleting agent rituximab in addition to standard methimazole-therapy prolongs remission. Paradoxically, it does not mediate a reduction in thyrotropin receptor antibody (TRAb) levels over that of methimazole monotherapy. Using a bioassay in...

  4. Phase 2 study of cladribine followed by rituximab in patients with hairy cell leukemia

    Science.gov (United States)

    O'Brien, Susan; Jorgensen, Jeffrey; Pierce, Sherry; Faderl, Stefan; Ferrajoli, Alessandra; Koller, Charles; Challagundla, Pramoda; York, Sergernne; Brandt, Mark; Luthra, Rajyalakshmi; Burger, Jan; Thomas, Deborah; Keating, Michael; Kantarjian, Hagop

    2011-01-01

    We conducted this study to determine the feasibility and safety of cladribine followed by rituximab in patients with hairy cell leukemia including the vari-ant form (HCLv). Cladribine 5.6 mg/m2 given IV over 2 hours daily for 5 days was followed ∼ 1 month later with rituximab 375 mg/m2 IV weekly for 8 weeks. Responses were recorded and BM minimal residual disease (MRD) was evaluated after the completion of rituximab. Thirty-six patients have been treated including 5 with HCLv. Median age was 57 years (range, 37-89). All patients (100%) have achieved complete response (CR), defined as presence of no hairy cells in BM and blood with normalization of counts (absolute neutrophil count [ANC]> 1.5 × 109/L, hemoglobin [Hgb] > 12.0 g/dL, platelets [PLT] > 100 × 109/L), as well as resolution of splenomegaly. There were no grade 3 or 4 nonhematologic adverse events directly related to the treatment. Only 1 patient (with HCLv) has relapsed; median CR duration has not been reached (range,1+-63+ months). Three patients with HCLv died including 1 with relapsed disease and 2 from unrelated malignancies. Median survival duration has not been reached (range, 2+-64+ months). Treatment with clad-ribine followed by rituximab is effective tk;4and may increase CR rate. This study was registered at www.clinicaltrials.gov as NCT00412594. PMID:21821712

  5. Fludarabine, cyclophosphamide, and rituximab chemoimmunotherapy is highly effective treatment for relapsed patients with CLL

    Science.gov (United States)

    Badoux, Xavier C.; Keating, Michael J.; Wang, Xuemei; O'Brien, Susan M.; Ferrajoli, Alessandra; Faderl, Stefan; Burger, Jan; Koller, Charles; Lerner, Susan; Kantarjian, Hagop

    2011-01-01

    Optimal management of patients with relapsed/refractory chronic lymphocytic leukemia (CLL) is dictated by patient characteristics, prior therapy, and response to prior therapy. We report the final analysis of combined fludarabine, cyclophosphamide, and rituximab (FCR) for previously treated patients with CLL and identify patients who benefit most from this therapy. We explore efficacy of FCR in patients beyond first relapse, patients with prior exposure to fludarabine and alkylating agent combinations, and patients with prior exposure to rituximab. The FCR regimen was administered to 284 previously treated patients with CLL. Patients were assessed for response and progression by 1996 National Cancer Institute–Working Group (NCI-WG) criteria for CLL and followed for survival. The overall response rate was 74%, with 30% complete remission. The estimated median overall survival was 47 months and median progression-free survival for all patients was 21 months. Subgroup analyses indicated that the following patients were most suitable for FCR treatment: patients with up to 3 prior treatments, fludarabine-sensitive patients irrespective of prior rituximab exposure, and patients without chromosome 17 abnormalities. FCR is an active and well-tolerated therapy for patients with relapsed CLL. The addition of rituximab to FC improved quality and durability of response in this patient population. PMID:21245487

  6. Two courses of rituximab (anti-CD20 monoclonal antibody) for recalcitrant pemphigus vulgaris

    DEFF Research Database (Denmark)

    Faurschou, A.; Gniadecki, R.

    2008-01-01

    Background Pemphigus vulgaris (PV) is a severe autoimmune blistering disease involving the skin and mucous membranes. The response to therapy varies greatly amongst patients and treatment may be challenging. Rituximab is a chimeric monoclonal antibody that selectively targets cell surface antigen...

  7. 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...

  8. 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 Joop

    2007-01-01

    CONTEXT: 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...

  9. Treatment of posttransplant lymphoproliferatieve disease with rituximab : The remission, the relapse, and the complication

    NARCIS (Netherlands)

    Verschuuren, EAM; Stevens, SJC; Van Imhoff, GW; Middeldorp, JM; De Boer, C; Koeter, G; The, TH; Van Der Bij, W

    2002-01-01

    Background. Rituximab, a humanized anti-CD20 monoclonal antibody, is a promising new tool for the treatment of posttransplant lymphoproliferative disease (PTLD), especially for patients transplanted with rejection prone transplants of vital organs, such as patients after lung transplantation. Thus f

  10. A series of patients with minimal change nephropathy treated with rituximab during adolescence and adulthood

    NARCIS (Netherlands)

    M.J. Dekkers (Marinus J.); J. Groothoff (Jaap); R. Zietse (Robert); M.G.H. Betjes (Michiel)

    2015-01-01

    textabstractBackground: The treatment of immune suppression dependent minimal change nephropathy (MCN) can be challenging and frequently leads to serious complications. In paediatric patients, successful treatment with rituximab is described in steroid-dependent MCN. There is limited information abo

  11. Salvage therapy for primary CNS lymphoma with a combination of rituximab and temozolomide

    NARCIS (Netherlands)

    Enting, Roeline; Demopoulos, A; DeAngelis, LM; Abrey, LE

    2004-01-01

    The authors evaluated the efficacy of a combination of rituximab and temozolomide for recurrent or refractory primary CNS lymphoma (PCNSL). Fifteen patients with a median age of 69 years had a 53% objective response rate with acceptable toxicity. Median overall survival is 14 months and median progr

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Institute of Scientific and Technical Information of China (English)

    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.

  14. Relapsing or refractory idiopathic thrombotic thrombocytopenic purpura-hemolytic uremic syndrome: the role of rituximab.

    Science.gov (United States)

    Caramazza, Domenica; Quintini, Gerlando; Abbene, Ignazio; Malato, Alessandra; Saccullo, Giorgia; Lo Coco, Lucio; Di Trapani, Rosa; Palazzolo, Roberto; Barone, Rita; Mazzola, Giuseppina; Rizzo, Sergio; Ragonese, Paolo; Aridon, Paolo; Abbadessa, Vincenzo; Siragusa, Sergio

    2010-12-01

    Idiopathic thrombotic thrombocytopenic purpura-hemolytic uremic syndrome (TTP-HUS) is a rare disease responsive to treatment with plasma exchange (PE) but with a high percentage of relapse or refractory patients. A severe deficiency of ADAMTS-13 (<5% of normal activity), congenital or caused by an autoantibody, may be specific for TTP and it has been proposed that severe ADAMTS-13 deficiency now defines TTP. B cells play a key role in both the development and the perpetuation of autoimmunity, suggesting that B-cell depletion could be a valuable treatment approach for patients with idiopathic TTP-HUS. This review of the literature focuses on the role of rituximab, a chimeric monoclonal antibody directed against CD20 antigen expressed by B lymphocytes, in patients with relapsing or refractory TTP-HUS with or without ADAMTS-13 deficiency, suggesting that rituximab may produce clinical remission in a significant proportion of patients. Rituximab therapy reduces plasma requirement and avoids complications related to salvage-immunosuppressive therapy. In conclusion, rituximab provides an effective, well-tolerated, and safe treatment option for patients with idiopathic TTP-HUS, thus giving an alternative approach to the current treatment based on PE.

  15. MRI assessment of suppression of structural damage in patients with rheumatoid arthritis receiving rituximab

    DEFF Research Database (Denmark)

    Peterfy, Charles; Emery, Paul; Tak, Paul P;

    2014-01-01

    OBJECTIVE: To evaluate changes in structural damage and joint inflammation assessed by MRI following rituximab treatment in a Phase 3 study of patients with active rheumatoid arthritis (RA) despite methotrexate (MTX) who were naive to biological therapy. METHODS: Patients were randomised to receive...

  16. Rituximab-induced depletion of anti-PLA2R autoantibodies predicts response in membranous nephropathy.

    Science.gov (United States)

    Beck, Laurence H; Fervenza, Fernando C; Beck, David M; Bonegio, Ramon G B; Malik, Fahim A; Erickson, Stephen B; Cosio, Fernando G; Cattran, Daniel C; Salant, David J

    2011-08-01

    Autoantibodies to the M-type phospholipase A(2) receptor (PLA(2)R) are sensitive and specific for idiopathic membranous nephropathy. The anti-B cell agent rituximab is a promising therapy for this disease, but biomarkers of early response to treatment currently do not exist. Here, we investigated whether levels of anti-PLA(2)R correlate with the immunological activity of membranous nephropathy, potentially exhibiting a more rapid response to treatment than clinical parameters such as proteinuria. We measured the amount of anti-PLA(2)R using Western blot immunoassay in serial serum samples from a total of 35 patients treated with rituximab for membranous nephropathy in two distinct cohorts. Pretreatment samples from 25 of 35 (71%) patients contained anti-PLA(2)R, and these autoantibodies declined or disappeared in 17 (68%) of these patients within 12 months after rituximab. Those who demonstrated this immunologic response fared better clinically: 59% and 88% attained complete or partial remission by 12 and 24 months, respectively, compared with 0% and 33% among those with persistent anti-PLA(2)R levels. Changes in antibody levels preceded changes in proteinuria. One subject who relapsed during follow-up had a concomitant return of anti-PLA(2)R. In summary, measuring anti-PLA(2)R levels by immunoassay may be a method to follow and predict response to treatment with rituximab in membranous nephropathy.

  17. ‘Les liaisons dangereuses’: Hepatitis C, Rituximab and B-cell non-Hodgkin’s lymphomas

    Institute of Scientific and Technical Information of China (English)

    Massimo; Marignani; Michela; di; Fonzo; Paola; Begini; Elia; Gigante; Ilaria; Deli; Adriano; M; Pellicelli; Sara; Gallina; Emanuela; de; Santis; Gianfranco; Delle; Fave; M; Christina; Cox

    2012-01-01

    Rituximab has provided a revolutionary contribution to the treatment of B-cell non-Hodgkin’s lymphomas (NHL). A high prevalence of hepatitis C virus (HCV) infection has been described in B-cell NHL patients. Cases of liver dysfunction in HCV-positive patients have been reported with Rituximab-containing regimens. In this paper we review the recent data regarding the effects of Rituximab in NHL patients with HCV infection. We also added a section devoted to improving communication between oncohaematologists and hepatologists. Furthermore, we propose a common methodological ground to study hepatic toxicity emerging during chemotherapy.

  18. Anti-Phospholipase A2 Receptor Antibody Titer Predicts Post-Rituximab Outcome of Membranous Nephropathy.

    Science.gov (United States)

    Ruggenenti, Piero; Debiec, Hanna; Ruggiero, Barbara; Chianca, Antonietta; Pellé, Timothee; Gaspari, Flavio; Suardi, Flavio; Gagliardini, Elena; Orisio, Silvia; Benigni, Ariela; Ronco, Pierre; Remuzzi, Giuseppe

    2015-10-01

    Rituximab induces nephrotic syndrome (NS) remission in two-thirds of patients with primary membranous nephropathy (MN), even after other treatments have failed. To assess the relationships among treatment effect, circulating nephritogenic anti-phospholipase A2 receptor (anti-PLA2R) autoantibodies and genetic polymorphisms predisposing to antibody production we serially monitored 24-hour proteinuria and antibody titer in patients with primary MN and long-lasting NS consenting to rituximab (375 mg/m(2)) therapy and genetic analyses. Over a median (range) follow-up of 30.8 (6.0-145.4) months, 84 of 132 rituximab-treated patients achieved complete or partial NS remission (primary end point), and 25 relapsed after remission. Outcomes of patients with or without detectable anti-PLA2R antibodies at baseline were similar. Among the 81 patients with antibodies, lower anti-PLA2R antibody titer at baseline (P=0.001) and full antibody depletion 6 months post-rituximab (hazard ratio [HR], 7.90; 95% confidence interval [95% CI], 2.54 to 24.60; PPLA2R antibody depletion. On average, 50% anti-PLA2R titer reduction preceded equivalent proteinuria reduction by 10 months. Re-emergence of circulating antibodies predicted disease relapse (HR, 6.54; 95% CI, 1.57 to 27.40; P=0.01), whereas initial complete remission protected from the event (HR, 6.63; 95% CI, 2.37 to 18.53; PPLA2R1 and HLA-DQA1 polymorphisms and of previous immunosuppressive treatment. Therefore, assessing circulating anti-PLA2R autoantibodies and proteinuria may help in monitoring disease activity and guiding personalized rituximab therapy in nephrotic patients with primary MN.

  19. Barriers to the Access and Use of Rituximab in Patients with Non-Hodgkin’s Lymphoma and Chronic Lymphocytic Leukemia: A Physician Survey

    Directory of Open Access Journals (Sweden)

    William H. Baer II

    2014-05-01

    Full Text Available Biologics such as rituximab are an important component of oncology treatment strategies, although access to such therapies is challenging in countries with limited resources. This study examined access to rituximab and identified potential barriers to its use in the United States, Mexico, Turkey, Russia, and Brazil. The study also examined whether availability of a biosimilar to rituximab would improve access to, and use of, rituximab. Overall, 450 hematologists and oncologists completed a survey examining their use of rituximab in patients with non-Hodgkin’s lymphoma (NHL and chronic lymphocytic leukemia (CLL. Less than 40% of physicians considered rituximab as easy to access from a cost perspective. Furthermore, many physicians chose not to treat, were unable to treat, or had to modify treatment with rituximab despite guidelines recommending its use in NHL and CLL patients. Insurance coverage, reimbursement, and cost to patient were commonly reported as barriers to the use of rituximab. Across all markets, over half of physicians reported that they would increase use of rituximab if a biosimilar was available. We conclude that rituximab use would increase across all therapy types and markets if a biosimilar was available, although a biosimilar would have the greatest impact in Brazil, Mexico, and Russia.

  20. Rituximab induced lung injury in a case of NHL: Diagnosis and follow up on FDG PET/CT

    Energy Technology Data Exchange (ETDEWEB)

    Joshi, Prathamesh; Lele, Vikram [Jaslok Hospital and Research Centre, Worli (United States); Saikia, Tapan [Prince Aly Khan Hospital, Mumbai (India)

    2012-09-15

    Rituximab induced lung injury is a rare but serious side effect of this agent. We describe the valuable role played by 18F fluorodeoxyglucose positron emission tomography computed tomography (FDG PET CT)in the diagnosis and follow up of this condition in a patient with non Hodgkin's lymphoma (NHL)receiving rituximab. Abnormal uptake of FDG in lungs of patients receiving this drug should be care fully evaluated to diagnose this potentially fatal side effect.

  1. Sustained complete remission of steroid- and cyclophosphamide-resistant minimal-change disease with a single course of rituximab therapy.

    Science.gov (United States)

    Janardan, Jyotsna; Ooi, Khai; Menahem, Solomon

    2014-06-01

    We report a case of steroid- and cyclophosphamide-resistant nephrotic syndrome secondary to minimal-change disease occurring in an otherwise healthy 19-year-old female, responding rapidly to two doses of rituximab therapy. Complete disease remission has been sustained up to last follow-up (32 months) despite CD19 recovery. Literature review suggests emerging evidence that rituximab may have a role to play in recurrent and/or refractory minimal-change disease.

  2. Sustained complete remission of steroid- and cyclophosphamide-resistant minimal-change disease with a single course of rituximab therapy

    OpenAIRE

    Janardan, Jyotsna; Ooi, Khai; Menahem, Solomon

    2014-01-01

    We report a case of steroid- and cyclophosphamide-resistant nephrotic syndrome secondary to minimal-change disease occurring in an otherwise healthy 19-year-old female, responding rapidly to two doses of rituximab therapy. Complete disease remission has been sustained up to last follow-up (32 months) despite CD19 recovery. Literature review suggests emerging evidence that rituximab may have a role to play in recurrent and/or refractory minimal-change disease.

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

    Directory of Open Access Journals (Sweden)

    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.

  4. Rituximab-induced interleukin-15 reduction associated with clinical improvement in rheumatoid arthritis

    Science.gov (United States)

    Díaz-Torné, César; Ortiz de Juana, M Angels; Geli, Carme; Cantó, Elisabet; Laiz, Ana; Corominas, Héctor; Casademont, Jordi; de Llobet, Josep M; Juárez, Cándido; Díaz-López, César; Vidal, Sílvia

    2014-01-01

    Rituximab therapy alters all aspects of B-cell participation in the disturbed immune response of rheumatoid arthritis patients. To determine the impact of B-cell depletion on other immune compartments, we analysed levels of soluble and surface interleukin-15 (IL-15) along with the frequency of IL-15-related subsets after rituximab treatment. We then studied the correlation of observed changes with clinical activity. Heparinized blood samples from 33 rheumatoid arthritis patients were collected on days 0, 30, 90 and 180 after each of three rituximab cycles. Serum cytokine levels were determined by ELISA. Interleukin-15 trans-presentation was analysed by cytometry. Flow cytometry with monoclonal antibodies was performed to analyse circulating cell subsets. Interleukin-15 was detected in the serum of 25 patients before initiating the treatment. Rituximab then progressively reduced serum IL-15 (138 ± 21 pg/ml at baseline, 48 ± 18 pg/ml after third cycle, P = 0·03) along with IL-17 (1197 ± 203 pg/ml at baseline, 623 ± 213 pg/ml after third cycle, P = 0·03) and tended to increase the frequency of circulating regulatory T cells (3·1 ± 1 cells/μl at baseline, 7·7 ± 2 cells/μl after third cycle). Rituximab also significantly decreased IL-15 trans-presentation on surface monocytes of patients negative for IL-15 serum (mean fluorescence intensity: 4·82 ± 1·30 at baseline, 1·42 ± 0·69 after third cycle P = 0·05). Reduction of serum IL-15 was associated with decrease in CD8+ CD45RO+/RA+ ratio (1·17 ± 0·21 at baseline, 0·36 ± 0·06 at third cycle, P = 0·02). DAS28, erythrocyte sedimentation rate and C-reactive protein correlated significantly with CD8+ CD45RO+/RA+ ratio (R = 0·323, R = 0·357, R = 0·369 respectively, P < 0·001). Our results suggest that sustained clinical improvement after rituximab treatment is associated with IL-15/memory T-cell-related mechanisms beyond circulating B cells. PMID:24219764

  5. Rituximab and escalated chemotherapy in elderly patients with aggressive diffuse large-cell lymphoma: a controlled clinical trial.

    Science.gov (United States)

    Avilés, Agustin; Nambo, María Jesus; Castañeda, Claudia; Cleto, Sergio; Neri, Natividad; Murillo, Edgar; Huerta-Guzmán, Judith; Contreras, Margarita

    2007-04-01

    The treatment of elderly patients with aggressive malignant lymphoma has not been defined. The addition of rituximab to conventional chemotherapy has been reported to improve the outcome, but most patients have good prognostic factors (performance status < 2, no severe associated diseases, low or low-intermediate clinical risk). Thus, we developed a combined regimen, including escalated doses of anthracycline and rituximab. The endpoint was to improve event-free survival (EFS) and overall survival. Two hundred and four (204) patients were randomly assigned to receive an escalated chemotherapy regimen (CEOP) with escalated dose of epirubicin, compared to the same regimen and addition of rituximab. All patients had poor prognostic factors: high- or high-intermediate clinical risk, poor performance status, bulky disease, and more than 2 with extranodal involvement. In an intent-to-treat analysis, all patients were evaluable for efficacy and toxicity. The complete response rates were similar in both arms: 74% in chemotherapy and 78% in the rituximab + chemotherapy program. EFS and overall survival were similar: 77% and 84%, respectively, in combined chemotherapy and 75% and 81% in the rituximab-chemotherapy regimen. Toxicity was mild and well tolerated. In elderly patients with diffuse large-cell lymphoma and poor prognostic factors, rituximab did not improve their outcome.

  6. Using health-system-wide data to understand hepatitis B virus prophylaxis and reactivation outcomes in patients receiving rituximab

    Science.gov (United States)

    Schmajuk, Gabriela; Tonner, Chris; Trupin, Laura; Li, Jing; Sarkar, Urmimala; Ludwig, Dana; Shiboski, Stephen; Sirota, Marina; Dudley, R. Adams; Murray, Sara; Yazdany, Jinoos

    2017-01-01

    Abstract Hepatitis B virus (HBV) reactivation in the setting of rituximab use is a potentially fatal but preventable safety event. The rate of HBV screening and proportion of patients at risk who receive antiviral prophylaxis in patients initiating rituximab is unknown. We analyzed electronic health record (EHR) data from 2 health systems, a university center and a safety net health system, including diagnosis grouper codes, problem lists, medications, laboratory results, procedures codes, clinical encounter notes, and scanned documents. We identified all patients who received rituximab between 6/1/2012 and 1/1/2016. We calculated the proportion of rituximab users with inadequate screening for HBV according to the Centers for Disease Control guidelines for detecting latent HBV infection before their first rituximab infusion during the study period. We also assessed the proportion of patients with positive hepatitis B screening tests who were prescribed antiviral prophylaxis. Finally, we characterized safety failures and adverse events. We included 926 patients from the university and 132 patients from the safety net health system. Sixty-one percent of patients from the university had adequate screening for HBV compared with 90% from the safety net. Among patients at risk for reactivation based on results of HBV testing, 66% and 92% received antiviral prophylaxis at the university and safety net, respectively. We found wide variations in hepatitis B screening practices among patients receiving rituximab, resulting in unnecessary risks to patients. Interventions should be developed to improve patient safety procedures in this high-risk patient population. PMID:28353614

  7. 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.

  8. 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.

  9. Rituximab-induced neutropenia in a patient with inflammatory myopathy and systemic sclerosis overlap disease.

    Science.gov (United States)

    Akram, Qasim; Roberts, Mark; Oddis, Chester; Herrick, Arianne; Chinoy, Hector

    2016-01-01

    Rituximab (RTX) is a monoclonal chimeric antibody directed against the CD20 antigen of B lymphocytes. Late onset neutropenia (LON) is a recognised complication of rituximab usually occurring 4 weeks after the last dose and is reported in both haematological and rheumatological conditions. However, it has never been described in a patient with myositis and systemic sclerosis overlap disease. We describe a case of LON in a 54-year-old man who was diagnosed with myositis and then systemic sclerosis overlap disease. It resolved within 7 days, and the patient did not suffer neutropenic sepsis or any other complications. We propose similar mechanisms for LON as described in other conditions and routine blood monitoring in such patients.

  10. Rituximab therapy for factor II inhibitor in a patient with antiphospholipid antibody syndrome.

    Science.gov (United States)

    Guddati, Achuta K; Kuter, David J

    2014-04-01

    Factor II inhibitors have been associated with an increased risk of bleeding. The management of patients with factor II inhibitors has not been adequately described. We describe a patient with an increased bleeding tendency due to factor II inhibitor who was unable to undergo surgery due to her bleeding tendency. The patient was successfully treated with a course of rituximab, which markedly reduced her factor II inhibitor: the factor II level rose from 12 to 61%; prothrombin time decreased from 20 to 14.7 s; and partial thromboplastin time (PTT) decreased from 148 to 38.8 s. She was able to undergo abdominal surgery without any hemorrhagic complications. This case exemplifies the possibility of treating patients with factor II inhibitors with rituximab therapy.

  11. 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.

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

    Science.gov (United States)

    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.

  13. Rituximabe para o tratamento da artrite reumatoide: revisão sistemática

    Directory of Open Access Journals (Sweden)

    Lívia Lovato Pires de Lemos

    2014-06-01

    Full Text Available Introdução: A artrite reumatoide (AR é uma doença autoimune crônica caracterizada por inflamação articular sistêmica que, com frequência, leva a significativa incapacitação. Vários agentes anti-TNF têm sido usados efetivamente, mas alguns pacientes demonstraram resposta inadequada. Rituximabe é um anticorpo monoclonal terapêutico indicado em tais casos. Métodos: Realizou-se uma revisão sistemática para avaliar a eficácia e a segurança de rituximabe em pacientes com AR ativa previamente tratados ou não com agentes anti-TNF e para relacionar o desfecho com a sorologia para FR e anti-CCP. Pesquisaram-se importantes bancos de dados eletrônicos e a literatura não convencional, além de se fazer uma busca manual de referências. Para a meta-análise, utilizou-se o programa Review Manager® 5.1. Resultados: Consideramos seis ERCs comparando rituximabe 1000 mg com placebo. Em ambos os grupos usou-se Metotrexato. O tratamento com rituximabe foi mais efetivo em pacientes jamais tratados e nos que não obtiveram sucesso com a terapia anti-TNF - critérios ACR 20/50/70 e EULAR. No grupo de rituximabe, observaram-se mudanças menos expressivas nos escores de Sharp/Genant, de erosão e de estreitamento do espaço articular; nesse grupo, os escores SF-36, FACIT-T e HAQ-DI também foram melhores. Não foram notadas diferenças entre grupos com relação aos desfechos de segurança, com exceção das reações agudas à infusão, que foram mais comuns no grupo de rituximabe. Ainda no grupo de rituximabe, um número maior de pacientes soropositivos para FR/anti-CCP alcançou ACR20, em comparação com pacientes negativos para RF/anti-CCP. Conclusão: Os dados disponíveis falam em favor do uso de rituximabe para o tratamento da AR, como opção efetiva e segura para pacientes jamais tratados ou que não obtiveram sucesso com o tratamento anti-TNF. FR e anti-CCP parecem influenciar os resultados do tratamento, mas essa inferência ainda est

  14. Severe multi-resistant pemphigus vulgaris: prolonged remission with a single cycle of rituximab.

    Science.gov (United States)

    Corral, Isabela Soubhia; Freitas, Thais Helena Proença de; Aquino, Renata Telles Rudge de; Koller, Daniella Abbruzzini S; Magliari, Maria Elisa Ruffolo; Muller, Helena

    2013-01-01

    Pemphigus vulgaris is an autoimmune bullous disease whose therapy is based on systemic corticosteroids, with or without immunosuppressants. Rituximab is a chimeric monoclonal antibody of the IgG class, directed at a specific CD20 B cell surface antigen, used in pemphigus vulgaris empirically since 2002, with success in 90% of the cases and long periods of remission. Male patient, 33 years old, diagnosed with pemphigus vulgaris, confirmed by histopathology and direct immunofluorescence. He was treated for seven months with numerous treatments, including immunosuppressive drugs, with an unsatisfactory response, until he had complete remission with the use of rituximab. During a 34-month follow-up period, the patient presented a slight clinical relapse, which was successfully controlled with prednisone in a daily dose of 120 mg, soon reduced to 20mg.

  15. First-line use of rituximab correlates with increased overall survival in late post-transplant lymphoproliferative disorders: retrospective, single-centre study.

    Science.gov (United States)

    Martínez-Calle, Nicolás; Alfonso, Ana; Rifón, José; Herrero, Ignacio; Errasti, Pedro; Rábago, Gregorio; Merino, Juana; Panizo, Ángel; Pardo, Javier; Prósper, Felipe; García-Muñoz, Ricardo; Lecumberri, Ramón; Panizo, Carlos

    2017-01-01

    This retrospective study evaluates the impact of rituximab on PTLD response and survival in a single-centre cohort. PTLD cases between 1984 and 2009, including heart, kidney, liver and lung transplant recipients, were included. Survival was analysed taking into account the type of PTLD (monomorphic vs. polymorphic), EBV infection status, IPI score, Ann Arbor stage and use of rituximab. Among 1335 transplanted patients, 24 developed PTLD. Median age was 54 yr (range 29-69), median time to diagnosis 50 months (range 0-100). PTLD type was predominantly late/monomorphic (79% and 75%), mostly diffuse large B-cell type. Overall response rate (ORR) was 62% (66% rituximab vs. 50% non-rituximab; P = 0.5). R-CHOP-like regimens were used most frequently (72% of patients treated with rituximab). Median overall survival was 64 months (CI 95% 31-96). OS was significantly increased in patients treated with rituximab (P = 0.01; CI 95% rituximab 58-79 months; non-rituximab 1-30 months). Post-transplant immunosuppression regimen had no effect on survival or time to PTLD, except for cyclosporine A (CyA), which associated with increased time to PTLD (P = 0.02). Rituximab was associated with increased survival in our single-centre series, and it should be considered as first-line therapy for PTLD patients. The possible protective effect of CyA for development of PTLD should be prospectively evaluated.

  16. Steroid-resistant autoimmune thrombocytopenia in systemic lupus erythematosus treated with rituximab

    Directory of Open Access Journals (Sweden)

    Vasudha V Sardesai

    2015-01-01

    Full Text Available Systemic Lupus Erythematosus (SLE is a multisystem disorder characterized by production of numerous autoantibodies, some of which have pathogenic consequences and result in considerable morbidity. Herein, we present a case of 48-year-old female with SLE having autoimmune hemolytic anemia, autoimmune thrombocytopenia, renal involvement, and recurrent flares of skin manifestations. She did not respond to the conventional therapy and was controlled and treated with Rituximab, a chimeric, monoclonal antiCD20 antibody, which specifically depletes B lymphocytes.

  17. Rituximab induces resolution of recurrent diffuse alveolar hemorrhage in a patient with primary antiphospholipid antibody syndrome.

    Science.gov (United States)

    Scheiman Elazary, A; Klahr, P P; Hershko, A Y; Dranitzki, Z; Rubinow, A; Naparstek, Y

    2012-04-01

    Diffuse alveolar hemorrhage (DAH) is a rare manifestation of primary antiphospholipid antibody syndrome (APS). We describe a patient with primary APS and refractory recurrent episodes of DAH. The patient was admitted 15 times due to recurrent episodes of DAH in a period of 18 months. Multiple immunosuppressive drugs did not improve his condition. Two years after his presentation, he was treated with rituximab (two doses of 1 g, 2 weeks apart). Six months later, the attacks of DAH have gradually disappeared. In a follow-up of more than 2 years after he received rituximab, the patient has had no further admissions due to DAH. Levels of antiphospholipid antibodies were measured during follow-up of 4 years. Anti-β2 glycoprotein IgG titer decreased to normal 6 months after therapy but anticardiolipin (aCL) antibody titer increased. We conclude that rituximab caused a dramatic clinical response in this patient. Anti-β2 glycoprotein IgG correlated better with the clinical response in this patient than aCL.

  18. Rituximab induces sustained reduction of pathogenic B cells in patients with peripheral nervous system autoimmunity

    Science.gov (United States)

    Maurer, Michael A.; Rakocevic, Goran; Leung, Carol S.; Quast, Isaak; Lukačišin, Martin; Goebels, Norbert; Münz, Christian; Wardemann, Hedda; Dalakas, Marinos; Lünemann, Jan D.

    2012-01-01

    The B cell–depleting IgG1 monoclonal antibody rituximab can persistently suppress disease progression in some patients with autoimmune diseases. However, the mechanism underlying these long-term beneficial effects has remained unclear. Here, we evaluated Ig gene usage in patients with anti–myelin-associated glycoprotein (anti-MAG) neuropathy, an autoimmune disease of the peripheral nervous system that is mediated by IgM autoantibodies binding to MAG antigen. Patients with anti-MAG neuropathy showed substantial clonal expansions of blood IgM memory B cells that recognized MAG antigen. The group of patients showing no clinical improvement after rituximab therapy were distinguished from clinical responders by a higher load of clonal IgM memory B cell expansions before and after therapy, by persistence of clonal expansions despite efficient peripheral B cell depletion, and by a lack of substantial changes in somatic hypermutation frequencies of IgM memory B cells. We infer from these data that the effectiveness of rituximab therapy depends on efficient depletion of noncirculating B cells and is associated with qualitative immunological changes that indicate reconfiguration of B cell memory through sustained reduction of autoreactive clonal expansions. These findings support the continued development of B cell–depleting therapies for autoimmune diseases. PMID:22426210

  19. Assessment of Physicochemical Properties of Rituximab Related to Its Immunomodulatory Activity

    Directory of Open Access Journals (Sweden)

    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.

  20. 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...... symptoms. A total of 133 patients were randomly assigned to either dexamethasone 40 mg/day for 4 days (n = 71) or in combination with rituximab 375 mg/m(2) weekly for 4 weeks (n = 62). Patients were allowed supplemental dexamethasone every 1 to 4 weeks for up to 6 cycles. Our primary end point, sustained...... response (ie, platelets ≥50×10(9)/L) at 6 months follow-up, was reached in 58% of patients in the rituximab + dexamethasone group vs 37% in the dexamethasone group (P = .02). The median follow-up time was 922 days. We found longer time to relapse (P = .03) and longer time to rescue treatment (P = .007...

  1. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Directory of Open Access Journals (Sweden)

    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.

  4. Rituximab Treatment for Membranous Nephropathy: A French Clinical and Serological Retrospective Study of 28 Patients

    Directory of Open Access Journals (Sweden)

    Pierre-Antoine Michel

    2011-12-01

    Full Text Available The development of well-tolerated and effective therapies that target the pathogenesis of membranous nephropathy (MN would be useful. Our objective was to evaluate the efficacy of rituximab in MN. We analyzed the outcome of 28 patients treated with rituximab for idiopathic MN. Anti-PLA2R antibodies in serum and PLA2R antigen in kidney biopsy were assessed in 10 and 9 patients, respectively. Proteinuria was significantly decreased by 56, 62 and 87% at 3, 6 and 12 months, respectively. At 6 months, 2 patients achieved complete remission (CR and 12 partial remission (PR; overall renal response, 50%. At 12 months (n = 23, CR was achieved in 6 patients and PR in 13 patients (overall renal response, 82.6%. Three patients suffered a relapse of nephrotic proteinuria 27–50 months after treatment. Univariate analysis suggested that the degree of renal failure (MDRD estimated glomerular filtration rate 2 is an independent factor that predicts lack of response to rituximab. Anti-PLA2R antibodies were detected in the serum of 10 patients, and PLA2R antigen in immune deposits in 8 of 9 patients. Antibodies became negative in all 5 responsive patients with available follow-up sera. In this retrospective study, a high rate of remission was achieved 12 months after treatment.

  5. Initial evaluation of {sup 227}Th-p-benzyl-DOTA-rituximab for low-dose rate {alpha}-particle radioimmunotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Dahle, Jostein [Department of Radiation Biology, Rikshospitalet-Radiumhospitalet HE, Montebello, 0310 Oslo (Norway)]. E-mail: jostein.dahle@labmed.uio.no; Borrebaek, Jorgen [Algeta ASA, Kjelsasveien 172 A, 0411 Oslo (Norway); Melhus, Katrine B. [Department of Radiation Biology, Rikshospitalet-Radiumhospitalet HE, Montebello, 0310 Oslo (Norway); Bruland, Oyvind S. [Department of Clinical Medicine, University of Oslo, 0316 Oslo (Norway); Department of Oncology, Rikshospitalet-Radiumhospitalet HE, Montebello, 0310 Oslo (Norway); Salberg, Gro [Algeta ASA, Kjelsasveien 172 A, 0411 Oslo (Norway); Olsen, Dag Rune [Department of Radiation Biology, Rikshospitalet-Radiumhospitalet HE, Montebello, 0310 Oslo (Norway); Larsen, Roy H. [Algeta ASA, Kjelsasveien 172 A, 0411 Oslo (Norway)

    2006-02-15

    Radioimmunotherapy has proven clinically effective in patients with non-Hodgkin's lymphoma. Radioimmunotherapy trials have so far been performed with {beta}-emitting isotopes. In contrast to {beta}-emitters, the shorter range and high linear energy transfer (LET) of {alpha} particles allow for more efficient and selective killing of individually targeted tumor cells. However, there are several obstacles to the use of {alpha}-particle immunotherapy, including problems with chelation chemistry and nontarget tissue toxicity. The {alpha}-emitting radioimmunoconjugate {sup 227}Th-DOTA-p-benzyl-rituximab is a new potential anti-lymphoma agent that might overcome some of these difficulties. The present study explores the immunoreactivity, in vivo stability and biodistribution, as well as the effect on in vitro cell growth, of this novel radioimmunoconjugate. To evaluate in vivo stability, uptake in balb/c mice of the {alpha}-particle-emitting nuclide {sup 227}Th alone, the chelated form, {sup 227}Th-p-nitrobenzyl-DOTA and the radioimmunoconjugate {sup 227}Th-DOTA-p-benzyl-rituximab was compared in a range of organs at increasing time points after injection. The immunoreactive fraction of {sup 227}Th-DOTA-p-benzyl-rituximab was 56-65%. During the 28 days after injection of radioimmunoconjugate only, very modest amounts of the {sup 227}Th had detached from DOTA-p-benzyl-rituximab, indicating a relevant stability in vivo. The half-life of {sup 227}Th-DOTA-p-benzyl-rituximab in blood was 7.4 days. Incubation of lymphoma cells with {sup 227}Th-DOTA-p-benzyl-rituximab resulted in a significant antigen-dependent inhibition of cell growth. The data presented here warrant further studies of {sup 227}Th-DOTA-p-benzyl-rituximab.

  6. Rituximab therapy in pulmonary alveolar proteinosis improves alveolar macrophage lipid homeostasis

    Directory of Open Access Journals (Sweden)

    Malur Anagha

    2012-06-01

    Full Text Available Abstract Rationale Pulmonary Alveolar Proteinosis (PAP patients exhibit an acquired deficiency of biologically active granulocyte-macrophage colony stimulating factor (GM-CSF attributable to GM-CSF specific autoantibodies. PAP alveolar macrophages are foamy, lipid-filled cells with impaired surfactant clearance and markedly reduced expression of the transcription factor peroxisome proliferator-activated receptor gamma (PPARγ and the PPARγ-regulated ATP binding cassette (ABC lipid transporter, ABCG1. An open label proof of concept Phase II clinical trial was conducted in PAP patients using rituximab, a chimeric murine-human monoclonal antibody directed against B lymphocyte specific antigen CD20. Rituximab treatment decreased anti-GM-CSF antibody levels in bronchoalveolar lavage (BAL fluid, and 7/9 patients completing the trial demonstrated clinical improvement as measured by arterial blood oxygenation. Objectives This study sought to determine whether rituximab therapy would restore lipid metabolism in PAP alveolar macrophages. Methods BAL samples were collected from patients pre- and 6-months post-rituximab infusion for evaluation of mRNA and lipid changes. Results Mean PPARγ and ABCG1 mRNA expression increased 2.8 and 5.3-fold respectively (p ≤ 0.05 after treatment. Lysosomal phospholipase A2 (LPLA2 (a key enzyme in surfactant degradation mRNA expression was severely deficient in PAP patients pre-treatment but increased 2.8-fold post-treatment. In supplemental animal studies, LPLA2 deficiency was verified in GM-CSF KO mice but was not present in macrophage-specific PPARγ KO mice compared to wild-type controls. Oil Red O intensity of PAP alveolar macrophages decreased after treatment, indicating reduced intracellular lipid while extracellular free cholesterol increased in BAL fluid. Furthermore, total protein and Surfactant protein A were significantly decreased in the BAL fluid post therapy. Conclusions Reduction in GM

  7. Dose dense (CEOP-14) vs dose dense and rituximab (CEOP-14 +R) in high-risk diffuse large cell lymphoma.

    Science.gov (United States)

    Avilés, Agustin; Nambo, María J; Neri, Natividad; Cleto, Sergio; Castañeda, Claudia; Huerta-Guzmàn, Judith; Murillo, Edgar; Contreras, Margarita; Talavera, Alejandra; González, Martha

    2007-01-01

    To assess efficacy and toxicity of rituximab and dose chemotherapy in high-risk diffuse large cell lymphoma, we conducted a controlled clinical trial to assess efficacy and toxicity of a dose-dense regimen CEOP- 14 (cyclophosphamide, epirubicin, vincristine, and prednisone every 14 d) compared to CEOP-14 plus rituximab. One hundred and ninety-six patients were randomized to received CEOP-rituximab (cyclophosphamide 1500 mg/m2, epirubicin 120 mg/m2, vincristine, and prednisone at standard dose and rituximab at 375 mg/m2) compared with the same chemotherapy administered every 14 d (CEOP-14). In an intent-to-treat analysis all patients were available for efficacy and toxicity. Complete response in CEOP-14 was observed in 73 cases (74%) and in 75 patients (76%) in the CEOP-R regimen (76%) (p = 0.8). With a median follow-up of 53.4 mo, median has not been reached in time to tumor-progression (TTP) and overall survival (OS). Actuarial curves at 5 yr showed that TTP and OS in patients treated with CEOP-R were 74% and 67%, respectively, that were not statistical different when compared to CEOP-14, 72% and 65%, respectively (p = 0.8). Acute toxicity was mild and well tolerated. The use of a dense-dose regimen is useful and well tolerated in patients with very high risk diffuse large cell lymphoma. The addition of rituximab did not improve outcome in these setting of patients.

  8. Phase I/II trial of everolimus in combination with bortezomib and rituximab (RVR) in relapsed/refractory Waldenstrom macroglobulinemia.

    Science.gov (United States)

    Ghobrial, I M; Redd, R; Armand, P; Banwait, R; Boswell, E; Chuma, S; Huynh, D; Sacco, A; Roccaro, A M; Perilla-Glen, A; Noonan, K; MacNabb, M; Leblebjian, H; Warren, D; Henrick, P; Castillo, J J; Richardson, P G; Matous, J; Weller, E; Treon, S P

    2015-12-01

    We examined the combination of the mammalian target of rapamycin inhibitor everolimus with bortezomib and rituximab in patients with relapsed/refractory Waldenstrom macroglobulinemia (WM) in a phase I/II study. All patients received six cycles of the combination of everolimus/rituximab or everolimus/bortezomib/rituximab followed by maintenance with everolimus until progression. Forty-six patients were treated; 98% received prior rituximab and 57% received prior bortezomib. No dose-limiting toxicities were observed in the phase I. The most common treatment-related toxicities of all grades were fatigue (63%), anemia (54%), leucopenia (52%), neutropenia (48%) and diarrhea (43%). Thirty-six (78%) of the 46 patients received full dose therapy (FDT) of the three drugs. Of these 36, 2 (6%) had complete response (90% confidence interval (CI): 1-16). In all, 32/36 (89%) of patients experienced at least a minimal response (90% CI: 76-96%). The observed partial response or better response rate was 19/36 (53, 90 CI: 38-67%). For the 36 FDT patients, the median progression-free survival was 21 months (95% CI: 12-not estimable). In summary, this study demonstrates that the combination of everolimus, bortezomib and rituximab is well tolerated and achieved 89% response rate even in patients previously treated, making it a possible model of non-chemotherapeutic-based combination therapy in WM.

  9. 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.

  10. Study of conjugation and radiolabeling of monoclonal antibody rituximab for use in radionuclide therapy; Estudo da conjugacao e radiomarcacao do anticorpo monoclonal rituximab para aplicacao em terapia radionuclidica

    Energy Technology Data Exchange (ETDEWEB)

    Massicano, Adriana Vidal Fernandes

    2011-07-01

    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 {sup 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

  11. 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

    DEFF Research Database (Denmark)

    Chatzidionysiou, Katerina; Lie, Elisabeth; Nasonov, Evgeny;

    2011-01-01

    To assess the 6-month effectiveness of the first rituximab (RTX) course in rheumatoid arthritis (RA) and to identify possible predictors of response.......To assess the 6-month effectiveness of the first rituximab (RTX) course in rheumatoid arthritis (RA) and to identify possible predictors of response....

  12. Comparison of the immunoreactivity of rituximab antibody labeled with either I-125 or Re-188 for radioimmunotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Choi, Tae Hyun; Chung, Hye Kyung; Lee, Tae Sup; Chung, Wee Sup; Woo, Kwang Sun; Lee, Myung Jin; Kim, So Yeon; Chung, Jae Ho; CHoi, Chang Woon; Lim, Sang Moo [KIRAMS, Seoul (Korea, Republic of); Darwati, Siti [National Nuclear Energy Agency, Tangerang (Indonesia)

    2004-07-01

    Monoclonal antibodies against tumor-associated antigens can be applied as delivery vehicles for radionuclides to treat tumors. The specificity of MAbs for tumor-associated antigens can be exploited to direct radionuclides selectively to tumor cells after systemic administration. In radioimmunotherapy, therapeutic efficacy depends on the choice of the radionuclide. The chemical characteristics of radioiodine and radiometals (Re-188) differ significantly with respect to labeling procedure and consequently the specificity of monoclonal antibody can be affected due to discrepancy of labeling condition. Rituximab is a genetically engineered, chimeric anti-CD20 monoclonal antibody with mouse variable and human constant region. The CD-20 itself plays an important role in human B-cell proliferation and is an effective target for immunotherapy. In the present study, we compared the immunoreactivity of I-125-labeled Rituximab with Re-188-labeled Rituximab according to radionuclide-optimized labeling condition in cell binding assay of Lindmo method.

  13. Venetoclax plus rituximab in relapsed or refractory chronic lymphocytic leukaemia: a phase 1b study

    Science.gov (United States)

    Seymour, John F; Ma, Shuo; Brander, Danielle M; Choi, Michael Y; Barrientos, Jacqueline; Davids, Matthew S; Anderson, Mary Ann; Beaven, Anne W; Rosen, Steven T; Tam, Constantine S; Prine, Betty; Agarwal, Suresh K; Munasinghe, Wijith; Zhu, Ming; Lash, L Leanne; Desai, Monali; Cerri, Elisa; Verdugo, Maria; Kim, Su Young; Humerickhouse, Rod A; Gordon, Gary B; Kipps, Thomas J; Roberts, Andrew W

    2017-01-01

    Summary Background Selective BCL2 inhibition with venetoclax has substantial activity in patients with relapsed or refractory chronic lymphocytic leukaemia. Combination therapy with rituximab enhanced activity in preclinical models. The aim of this study was to assess the safety, pharmacokinetics, and activity of venetoclax in combination with rituximab. Methods Adult patients with relapsed or refractory chronic lymphocytic leukaemia (according to the 2008 Modified International Workshop on CLL guidelines) or small lymphocytic lymphoma were eligible for this phase 1b, dose-escalation trial. The primary outcomes were to assess the safety profile, to determine the maximum tolerated dose, and to establish the recommended phase 2 dose of venetoclax when given in combination with rituximab. Secondary outcomes were to assess the pharmacokinetic profile and analyse efficacy, including overall response, duration of response, and time to tumour progression. Minimal residual disease was a protocol-specified exploratory objective. Central review of the endpoints was not done. Venetoclax was dosed daily using a stepwise escalation to target doses (200–600 mg) and then monthly rituximab commenced (375 mg/m2 in month 1 and 500 mg/m2 in months 2–6). Adverse events were graded according to the National Cancer Institute Common Terminology Criteria for adverse events version 4.0. Protocol-guided drug cessation was allowed for patients who achieved complete response (including complete response with incomplete marrow recovery) or negative bone marrow minimal residual disease. Analyses were done per protocol for all patients who commenced drug and included all patients who received at least one dose of venetoclax. Data were pooled across dose cohorts. Patients are still receiving therapy and follow-up is ongoing. The trial is registered at ClinicalTrials.gov, number NCT01682616. Findings Between Aug 6, 2012, and May 28, 2014, we enrolled 49 patients. Common grade 1–2 toxicities

  14. 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

  15. Comparative Study on Rituximab Combined with Chemotherapy and Single Chemotherapy for Diffuse Large B Cell Lymphoma

    Institute of Scientific and Technical Information of China (English)

    FENG Ji-feng

    2015-01-01

    Objective:To explore the clinical efifcacy and safety of rituximab combined with chemotherapy and single chemotherapy for diffuse large B cell lymphoma (DLBCL). Methods:A total of 97 patients with DLBCL were selected. Patients treated by single chemotherapy were designed as control group, while those by rituximab combined with chemotherapy as observational group. All patients were treated for at least 4 cycles. The short-term and long-term efifcacy and related adverse reactions of 2 groups were observed. Results:The rate of complete remission (CR) in observational group was signiifcantly higher than in control group (χ2=4.6589,P=0.0309). However, there was no signiifcant difference in objective remission rate (ORR) between 2 groups (P=0.3651). The rates of 3-year overall survival (OS), progression-free survival (PFS) and disease-free survival (DFS) were 80.30% (53/66), 69.70% (46/66) and 59.09% (39/66) in observational group, and 61.29% (19/31), 58.06% (18/31) and 58.06% (18/31) in control group, respectively. The OS in observational group was signiifcantly longer than in control group (P=0.035). However, there was no signiifcant difference in PFS, DFS and rate adverse reactions between 2 groups (P=0.089;P=0.438;χ2=0.1562,P=0.6927). Conclusion: Rituximab combined with chemotherapy can improve the efficacy of DLBCL without increasing the adverse reactions, which can be used as the ifrst-line treatment for DLBCL, thus deserving to be widely applied in clinic.

  16. Comparative Study on Rituximab Combined with Chemotherapy and Single Chemotherapy for Diffuse Large B Cell Lymphoma

    Directory of Open Access Journals (Sweden)

    Ji-feng FENG

    2015-06-01

    Full Text Available Objective: To explore the clinical efficacy and safety of rituximab combined with chemotherapy and single chemotherapy for diffuse large B cell lymphoma (DLBCL. Methods: A total of 97 patients with DLBCL were selected. Patients treated by single chemotherapy were designed as control group, while those by rituximab combined with chemotherapy as observational group. All patients were treated for at least 4 cycles. The short-term and long-term efficacy and related adverse reactions of 2 groups were observed. Results: The rate of complete remission (CR in observational group was significantly higher than in control group (χ2=4.6589, P=0.0309. However, there was no significant difference in objective remission rate (ORR between 2 groups (P=0.3651. The rates of 3-year overall survival (OS, progression-free survival (PFS and disease-free survival (DFS were 80.30% (53/66, 69.70% (46/66 and 59.09% (39/66 in observational group, and 61.29% (19/31, 58.06% (18/31 and 58.06% (18/31 in control group, respectively. The OS in observational group was significantly longer than in control group (P=0.035. However, there was no significant difference in PFS, DFS and rate adverse reactions between 2 groups (P=0.089; P=0.438; χ2=0.1562, P=0.6927. Conclusion: Rituximab combined with chemotherapy can improve the efficacy of DLBCL without increasing the adverse reactions, which can be used as the first-line treatment for DLBCL, thus deserving to be widely applied in clinic.

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

    DEFF Research Database (Denmark)

    El Fassi, D; Nielsen, Claus Henrik; Junker, Michael Peter;

    2011-01-01

    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...... 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...

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

    DEFF Research Database (Denmark)

    Rydén-Aulin, Monica; Boumpas, Dimitrios; 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...

  19. Efficacy of rituximab in gastric diffuse large B cell lymphoma patients

    Institute of Scientific and Technical Information of China (English)

    Davide; Leopardo; Giuseppe; Di; Lorenzo; Amalia; De; Renz

    2010-01-01

    AIM:To evaluate retrospectively the efficacy of rituximab plus chemotherapy in gastric diffuse large B cell lymphoma(DLBCL).METHODS:Sixty patients(median age:58 years)with histologically confirmed gastric DLBCL treated at four Italian institutions between 2000 and 2007,were included in this analysis.Patients were selected by stage (Ⅰ-Ⅳ,Lugano staging system),European Cooperative Oncology Group performance status(0-2)and treatment strategies.Treatment strategies were chemotherapy alone(group A,n=30)[schedule...

  20. Severe autoimmune hemolytic anemia after unrelated umbilical cord blood transplant for familial hemophagocytic lymphohistiocytosis: significant improvement after treatment with rituximab.

    Science.gov (United States)

    Radhi, Mohamed; Rumelhart, Steve; Tatman, David; Goldman, Fred

    2007-02-01

    A 4-month-old girl diagnosed with familial hemophagocytic lymphohistiocytosis underwent a matched unrelated, umbilical cord blood transplant. Six weeks later she developed severe acute autoimmune hemolytic anemia and thrombocytopenia requiring multiple transfusions. This was refractory to high-dose steroid and intravenous immunoglobulin, but did respond to Rituximab (anti-CD20 monoclonal antibody) 375 mg/m2. Hemolysis recurred after steroid tapering but responded to a second course of Rituximab. This case report highlights the difficulty in managing posttransplant autoimmune hemolytic anemia.

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

    DEFF Research Database (Denmark)

    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......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...

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

    Directory of Open Access Journals (Sweden)

    Esther de Vries

    2011-09-01

    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.

  3. Rituximab maintenance improves clinical outcome of relapsed/resistant follicular non-Hodgkin lymphoma in patients both with and without rituximab during induction: results of a prospective randomized phase 3 intergroup trial

    NARCIS (Netherlands)

    M.H.J. van Oers; R. Klasa; R.E. Marcus; M. Wolf; E. Kimby; R.D. Gascoyne; A. Jack; M. van't Veer; A. Vranovsky; H. Holte; M. van Glabbeke; I. Teodorovic; C. Rozewicz; A. Hagenbeek

    2006-01-01

    We evaluated the role of rituximab (R) both in remission induction and maintenance treatment of relapsed/resistant follicular lymphoma (FL). A total of 465 patients were randomized to induction with 6 cycles of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) (every 3 weeks) or R-CH

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

    Directory of Open Access Journals (Sweden)

    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.

  5. Rituximab therapy for flare-up of rheumatoid arthritis after total knee replacement surgery.

    Science.gov (United States)

    Mirza, Rabeea; Ishaq, Saliha; Khan, Muhammad Owais; Memon, Adil

    2012-10-01

    A variety of drug types are used alone or in combination to manage Rheumatoid Arthritis along with physiotherapy. We report herein the case of a 51 year old female patient with a history of Rheumatoid Arthritis whose disease remained active despite being on routinely used multiple disease modifying antirheumatic drugs. The patient underwent bilateral total knee arthroplasty with subtotal synovectomy due to the severe pain caused by her concomitant age related osteoarthritis which was only aggravated by her active rheumatoid arthritis disease. Three months following surgery, the patient's knee pain with typical rheumatoid flare and swelling reappeared for which a B cell monoclonal antibody, rituximab, was given. Her number of tender and swollen joints reduced to less than three and her C-reactive protein levels and erythrocyte sedimentation rate reduced significantly along with considerable improvement in her Global Assessment score. Her severity of pain also decreased to 3 from an initial score of 8 on the Visual Analog Scale. Thus, Rituximab helped improve our patient's symptoms from recurrence of synovitis after total knee replacement.

  6. Cyclophosphamide, fludarabine, alemtuzumab, and rituximab as salvage therapy for heavily pretreated patients with chronic lymphocytic leukemia

    Science.gov (United States)

    Badoux, Xavier C.; Keating, Michael J.; Wang, Xuemei; O'Brien, Susan M.; Ferrajoli, Alessandra; Faderl, Stefan; Burger, Jan; Koller, Charles; Lerner, Susan; Kantarjian, Hagop

    2011-01-01

    Patients with relapsed chronic lymphocytic leukemia (CLL) and high-risk features, such as fludarabine refractoriness, complex karyotype, or abnormalities of chromosome 17p, experience poor outcomes after standard fludaradine-based regimens. Alemtuzumab is a chimeric CD52 monoclonal antibody with activity in CLL patients with fludarabine-refractory disease and 17p deletion. We report the outcome for 80 relapsed or refractory patients with CLL enrolled in a phase 2 study of cyclophosphamide, fludarabine, alemtuzumab, and rituximab (CFAR). All patients were assessed for response and progression according to the 1996 CLL-working group criteria. For the intention-to-treat analysis, the overall response rate was 65%, including 29% complete response. The estimated progression-free survival was 10.6 months and median overall survival was 16.7 months. Although we noted higher complete response in high-risk patients after CFAR compared with a similar population who had received fludarabine, cyclophosphamide, and rituximab as salvage therapy, there was no significant improvement in progression-free survival and overall survival appeared worse. CFAR was associated with a high rate of infectious complications with 37 patients (46%) experiencing a serious infection during therapy and 28% of evaluable patients experiencing late serious infections. Although CFAR produced good response rates in this highly pretreated high-risk group of patients, there was no benefit in survival outcomes. PMID:21670470

  7. Rituximab plus liposomal doxorubicin in HIV-infected patients with KSHV-associated multicentric Castleman disease

    Science.gov (United States)

    Polizzotto, Mark N.; Aleman, Karen; Wyvill, Kathleen M.; Marshall, Vickie; Whitby, Denise; Wang, Victoria; Pittaluga, Stefania; O’Mahony, Deirdre; Steinberg, Seth M.; Little, Richard F.; Yarchoan, Robert

    2014-01-01

    Kaposi sarcoma (KS) herpesvirus–associated multicentric Castleman disease (KSHV-MCD) is a lymphoproliferative disorder, most commonly seen in HIV-infected patients, that has a high mortality if untreated. Concurrent KS is common. Although rituximab has reported activity in KSHV-MCD, its use is often associated with KS progression. Within a natural history study of KSHV-MCD, we prospectively evaluated rituximab 375 mg/m2 combined with liposomal doxorubicin 20 mg/m2 (R-Dox) every 3 weeks in 17 patients. Patients received a median of 4 cycles (range 3-9). All received antiretroviral therapy, 11 received consolidation interferon-α, and 6 received consolidation high-dose zidovudine with valganciclovir. Using NCI KSHV-MCD response criteria, major clinical and biochemical responses were attained in 94% and 88% of patients, respectively. With a median 58 months’ potential follow-up, 3-year event-free survival was 69% and 3-year overall survival was 81%. During R-Dox therapy, cutaneous KS developed in 1 patient, whereas 5 of 6 patients with it had clinical improvement. R-Dox was associated with significant improvement in anemia and hypoalbuminemia. KSHV viral load, KSHV viral interleukin-6, C-reactive protein, human interleukin-6, and serum immunoglobulin free light chains decreased with therapy. R-Dox is effective in symptomatic KSHV-MCD and may be useful in patients with concurrent KS. This trial was registered at www.clinicaltrials.gov as #NCT00092222. PMID:25331113

  8. Obinutuzumab: A Review in Rituximab-Refractory or -Relapsed Follicular Lymphoma.

    Science.gov (United States)

    Dhillon, Sohita

    2017-03-21

    Obinutuzumab (Gazyva(®), Gazyvaro(®)) is a recombinant, monoclonal, humanized and glycoengineered, type II, anti-CD20, IgG1 antibody. It has recently been granted an additional indication for the treatment of patients with follicular lymphoma who relapsed after, or are refractory to, a rituximab-containing regimen. In the primary analysis of the large, phase III GADOLIN study, induction therapy with obinutuzumab plus bendamustine followed by obinutuzumab maintenance prolonged progression-free survival (PFS) to a statistically significant extent relative to induction with bendamustine monotherapy in patients with indolent non-Hodgkin's lymphoma (iNHL). The improvement in PFS was largely driven by the subgroup of patients with follicular lymphoma, who also had prolonged overall survival (OS) in a planned updated analysis. Obinutuzumab had a generally manageable tolerability profile in these patients; mild to moderate infusion-related reactions (IRRs) were the most common treatment-emergent adverse events (AEs) and neutropenia the most common grade 3 or 4 treatment-related AEs. Although additional studies and longer-term data are needed to further assess treatment benefits with obinutuzumab, current evidence indicates that obinutuzumab is a useful treatment option for patients with rituximab-refractory or -relapsed follicular lymphoma.

  9. Neuromyelitis optica: Contribution of therapeutic responses markers monitoring in patients given rituximab.

    Science.gov (United States)

    Romero, G; Ticchioni, M; Cohen, M; Rosenthal-Allieri, M A; Mondot, L; Lebrun Frenay, C

    2016-03-01

    Neuromyelitis optica (NMO) is a central nervous system inflammatory autoimmune disease characterized by medullary and/or optical nerve damage. It is rare but life-threatening. Concerning the treatment of NMO, many drugs have been used in background therapy. Some studies have shown efficacy of rituximab (an antiCD20 monoclonal anti-body) either on the reduction of the annual number of exacerbation or the mean score EDSS. In 2013, a Korean team reported a new protocol during which they administered rituximab only when memory B lymphocytes CD27+ were detectable in the bloodstream. In our patient, institution of this protocol led to clinical benefit with a major decrease in the EDSS score over time (7 in August 2012 vs. 1 in October 2015), a reduction of the total administered dose (4g in 2013 vs. 1.375g in 2014 vs. 0g in 2015) and side effects. Compared with the rate of theoretical administration, health expenditure savings reached 1700 Euros per month over the 11-month treatment. Monitoring therapeutic response markers with memory B lymphocyte counts appear to be an efficient cost-effective way to measure clinical efficiency, reduce total doses, and limit side effects.

  10. Is rituximab effective for induction of remission in ANCA-associated vasculitis?

    Directory of Open Access Journals (Sweden)

    Carmen Rain

    2015-08-01

    Full Text Available La adición de rituximab al tratamiento con corticoides se ha planteado como alternativa terapéutica para inducir remisión en las vasculitis asociadas a anticuerpos anticitoplasma de neutrófilos (ANCA, especialmente en pacientes con deseo de preservar fertilidad que persisten activos después del tratamiento estándar, o en aquellos que tienen contraindicación o mala tolerancia a ciclofosfamida. Utilizando la base de datos Epistemonikos, la cual es mantenida mediante búsquedas en 30 bases de datos, identificamos solo una revisión sistemática que incluye tres estudios aleatorizados. Realizamos un metanálisis y tablas de resumen de los resultados utilizando el método GRADE. Concluimos que el uso de rituximab podría resultar en poca o nula diferencia en mortalidad, mientras que existe incertidumbre sobre si disminuye las recaídas o aumenta los efectos adversos serios, como infecciones o neoplasias.

  11. Common variable immunodeficiency unmasked by treatment of immune thrombocytopenic purpura with Rituximab

    DEFF Research Database (Denmark)

    Mogensen, Trine H; Jensen, Jens Magnus Bernth; Petersen, Charlotte C;

    2013-01-01

    BACKGROUND: Hypogammaglobulinemia may be part of several different immunological or malignant conditions, and its origin is not always obvious. Furthermore, although autoimmune cytopenias are known to be associated with common variable immunodeficiency (CVID) and even may precede signs of immunod......BACKGROUND: Hypogammaglobulinemia may be part of several different immunological or malignant conditions, and its origin is not always obvious. Furthermore, although autoimmune cytopenias are known to be associated with common variable immunodeficiency (CVID) and even may precede signs...... of immunodeficiency, this is not always recognized. Despite novel insight into the molecular immunology of common variable immunodeficiency, several areas of uncertainty remain. In addition, the full spectrum of immunological effects of the B cell depleting anti-CD20 antibody Rituximab has not been fully explored....... To our knowledge this is the first report of development of CVID in a patient with normal immunoglobulin prior to Rituximab treatment. CASE PRESENTATION: Here we describe the highly unusual clinical presentation of a 34-year old Caucasian male with treatment refractory immune thrombocytopenic purpura...

  12. Use of Rituximab in Autoimmune Hemolytic Anemia Associated with Non-Hodgkin Lymphomas

    Directory of Open Access Journals (Sweden)

    Claudio Fozza

    2011-01-01

    Full Text Available The association between non-Hodgkin lymphomas and autoimmune disorders is a well-known event. Also autoimmune hemolytic anemia (AHA, although much more frequent in patients with chronic lymphocytic leukemia (CLL, has been described in this group of patients. In recent years, among the more traditional therapeutic options, rituximab, an anti-CD20 monoclonal antibody, has shown interesting results in the treatment of primary AHA. Although this drug has been frequently used for AHA in patients with CLL, much less data are available on its use in NHL patients. However, considering that the main pathogenetic mechanism of AHA in course of lymphoproliferative disorders seems to be an antibody production directly or indirectly mediated by the neoplastic clone, this monoclonal antibody represents an ideal therapeutic approach. In this paper we will briefly describe some biological and clinical features of NHL-patients with AHA. We will then analyze some studies focusing on rituximab in primary AHA, finally reviewing the available literature on the use of this drug in NHL related AHA.

  13. Efficacy of a rituximab regimen based on B cell depletion in thrombotic thrombocytopenic purpura with suboptimal response to standard treatment: Results of a phase II, multicenter noncomparative study.

    Science.gov (United States)

    Benhamou, Ygal; Paintaud, Gilles; Azoulay, Elie; Poullin, Pascale; Galicier, Lionel; Desvignes, Céline; Baudel, Jean-Luc; Peltier, Julie; Mira, Jean-Paul; Pène, Frédéric; Presne, Claire; Saheb, Samir; Deligny, Christophe; Rousseau, Alexandra; Féger, Frédéric; Veyradier, Agnès; Coppo, Paul

    2016-12-01

    The standard four-rituximab infusions treatment in acquired thrombotic thrombocytopenic purpura (TTP) remains empirical. Peripheral B cell depletion is correlated with the decrease in serum concentrations of anti-ADAMTS13 and associated with clinical response. To assess the efficacy of a rituximab regimen based on B cell depletion, 24 TTP patients were enrolled in this prospective multicentre single arm phase II study and then compared to patients from a previous study. Patients with a suboptimal response to a plasma exchange-based regimen received two infusions of rituximab 375 mg m(-2) within 4 days, and a third dose at day +15 of the first infusion if peripheral B cells were still detectable. Primary endpoint was the assessment of the time required to platelet count recovery from the first plasma exchange. Three patients died after the first rituximab administration. In the remaining patients, the B cell-driven treatment hastened remission and ADAMTS13 activity recovery as a result of rapid anti-ADAMTS13 depletion in a similar manner to the standard four-rituximab infusions schedule. The 1-year relapse-free survival was also comparable between both groups. A rituximab regimen based on B cell depletion is feasible and provides comparable results than with the four-rituximab infusions schedule. This regimen could represent a new standard in TTP. This trial was registered at www.clinicaltrials.gov (NCT00907751). Am. J. Hematol. 91:1246-1251, 2016. © 2016 Wiley Periodicals, Inc.

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

    DEFF Research Database (Denmark)

    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...

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

    Science.gov (United States)

    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.

  16. A combination therapy with fludarabine, mitoxantrone and rituximab induces complete immunophenotypical remission in B-cell prolymphocytic leukaemia

    OpenAIRE

    Tempescul, Adrian; Feuerbach, Johanna; Ianotto, Jean-Christophe; Dalbies, Florence; Marion, Veronique; Bris, Marie-Josée; De Braekeleer, Marc; Berthou, Christian

    2008-01-01

    A combination therapy with fludarabine, mitoxantrone and rituximab induces complete immunophenotypical remission in B-cell prolymphocytic leukaemia phone: +33-298-223504 (Tempescul, Adrian) (Tempescul, Adrian) Department of Clinical Hematology, Institute of Cancerology and Hematology - CHU Morvan, Avenue Foch - 29609 - Brest - FRANCE (Tempescul, Adrian) Department of Clinical Hematology, Institute of Cancerology and Hematology - CHU Morvan, Avenue Foch - 2...

  17. Efficacy and safety of low-dose rituximab combined with different dosage of glucocorticoids for immune thrombocytopenia

    Institute of Scientific and Technical Information of China (English)

    邢伟伟

    2013-01-01

    Objective To compare the efficacy and safety of low-dose rituximab combined with different dosage of glucocorticoids for immune thrombocytopenia (ITP) .Methods Seventy-four patients (35 male,median age 34years,range 18—70 years) including 60 newly-diagnosed,6 persistent,5 chronic and 3 refractory patients

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

    DEFF Research Database (Denmark)

    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...

  19. Effectiveness of two different doses of rituximab for the treatment of rheumatoid arthritis in an international cohort

    DEFF Research Database (Denmark)

    Chatzidionysiou, Katerina; Lie, Elisabeth; Nasonov, Evgeny;

    2016-01-01

    BACKGROUND: The approved dose of rituximab (RTX) in rheumatoid arthritis is 1000 mg × 2, but some data have suggested similar clinical efficacy with 500 mg × 2. The purpose of this study was to compare the effectiveness of the regular and low doses given as first treatment course. METHODS: Twelve...

  20. Effects and safety of rituximab in systemic sclerosis : An analysis from the European Scleroderma Trial and Research (EUSTAR) group

    NARCIS (Netherlands)

    Jordan, Suzana; Distler, Jörg H W; Maurer, Britta; Huscher, Dörte; Van Laar, Jacob M.; Allanore, Yannick; Distler, Oliver; Kvien, Tore K.; Airo, Paolo; Sancho, Juan José Alegre; Ananjeva, Lidia; Ancuta, Codrina Michaela; Aringer, Martin; Balbir-Gurman, Alexandra; Cantatore, Francesco Paolo; Caramaschi, Paola; Chatelus, Emmanuel; Codullo, Veronica; Farge-Bancel, Dominique; Foti, Rosario; Gabrielli, Armando; Henes, Jörg; Herrgott, Ilka; Iannone, Florenzo; Ingegnoli, Francesca; Loyo, Esthela; Matucci-Cerinić, Marco; Mohamed, Walid Ahmed Abdel Atty; Müller-Ladner, Ulf; Palm, Øyvind; Popa, Sergiu; Riemekasten, Gabriela; Rednic, Simona; Rosato, Edoardo; Saracco, Marta; Scheja, Agneta; Smith, Vanessa; Mihai, Carina; Szucs, Gabriela; Tomšić, Matija; Valentini, Gabriele; Walker, Ulrich A.; Westhovens, Rene; Yavuz, Sule Kurhan; Zenone, Thierry

    2015-01-01

    Objectives: To assess the effects of Rituximab (RTX) on skin and lung fibrosis in patients with systemic sclerosis (SSc) belonging to the European Scleroderma Trial and Research (EUSTAR) cohort and using a nested case-control design. Methods: Inclusion criteria were fulfilment of American College of

  1. Rituximab Can Induce Remission in a Patient with Ankylosing Spondylitis Who Failed Anti-TNF-α Agent

    Science.gov (United States)

    AlDhaheri, Fahmi; Almteri, Talal; Dwid, Naji; Majdali, Ahd; Janoudi, Nahed; Almoallim, Hani

    2017-01-01

    Patient: Male, 38 Final Diagnosis: Ankylosing spondylitis Symptoms: Back pain • morning stiffness Medication: — Clinical Procedure: Not applicable Specialty: Rheuamatology Objective: Unusual or unexpected effect of treatment Background: Ankylosing spondylitis (AS) is a chronic inflammatory disease that predominantly affects the axial skeleton. The ability of anti-TNF-α agents to reduce disease activity in patients with axial spondyloarthritis (axSpA), including AS, has been demonstrated in multiple randomized trials and several meta-analyses. Reports on the efficacy of rituximab in treatment of AS have described good results. We report on a patient with AS who failed anti-TNF-α therapy but showed good clinical improvement with rituximab therapy. Case Report: A 38-year-old male patient was diagnosed with AS and showed poor response to sulfasalazine and non-steroidal anti-inflammatory drugs (NSAIDs). Infliximab was initiated with marked improvement as per the Bath ankylosing spondylitis disease activity index (BASDAI). Due to disease flare, the patient was switched to etanercept. He subsequently acquired papillary thyroid cancer and etanercept was discontinued. He underwent a total thyroidectomy followed by radioiodine therapy. For his ongoing active disease, NSAIDs and sulfasalazine were resumed with a lack of response (BASDAI=7.1). Rituximab was started and resulted in significant improvement (BASDAI=2.3). Conclusions: Rituximab can be a potential target therapy for patients who start to lose response to TNF-inhibitors or for those who develop solid malignancies. Further placebo-controlled studies are required. PMID:28179619

  2. Responsiveness of disease activity indices ESSPRI and ESSDAI in patients with primary Sjogren's syndrome treated with rituximab

    NARCIS (Netherlands)

    Meiners, P. M.; Arends, S.; Brouwer, E.; Spijkervet, F. K. L.; Vissink, A.; Bootsma, H.

    2012-01-01

    Objective To evaluate the responsiveness of the EULAR Sjogren's Syndrome Patient Reported Index (ESSPRI) and EULAR Sjogren's Syndrome Disease Activity Index (ESSDAI) in patients with primary Sjogren's syndrome (pSS) treated with rituximab. Methods Twenty-eight patients with pSS treated with rituxima

  3. Changes in salivary gland immunohistology and function after rituximab monotherapy in a patient with Sjogren's syndrome and associated MALT lymphoma

    NARCIS (Netherlands)

    Pijpe, J; van Imhoff, GW; Vissink, A; van der Wal, JE; Kluin, PM; Spijkervet, FKL; Kallenberg, CGM; Bootsma, H

    2005-01-01

    Objectives: To report the successful use of rituximab on salivary gland immunohistology and function in a patient with Sjogren's syndrome ( SS) and associated MALT lymphoma. Case report: The patient was a 42 year old woman with primary SS and associated MALT lymphoma located in the parotid gland and

  4. 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 br...

  5. Repeated injections of {sup 131}I-rituximab show patient-specific stable biodistribution and tissue kinetics

    Energy Technology Data Exchange (ETDEWEB)

    Antonescu, Cristian; Bischof Delaloye, Angelika; Schaffland, Andreas O.; Grannavel, Carine [University Hospital of Lausanne, Service of Nuclear Medicine, Lausanne (Switzerland); Kosinski, Marek [University Hospital of Lausanne, Service of Nuclear Medicine, Lausanne (Switzerland); University of Lausanne, Institute of Applied Radiophysics, Lausanne (Switzerland); Monnin, Pascal; Verdun, Francis R. [University of Lausanne, Institute of Applied Radiophysics, Lausanne (Switzerland); Ketterer, Nicolas [University Hospital of Lausanne, Multidisciplinary Oncology Center, Lausanne (Switzerland); Kovacsovics, Tibor [Oregon Health and Science University, Center for Hematological Malignancies, Portland, OR (United States); Buchegger, Franz [University Hospital of Lausanne, Service of Nuclear Medicine, Lausanne (Switzerland); University Hospital of Geneva, Service of Nuclear Medicine, Geneva (Switzerland)

    2005-08-01

    It is generally assumed that the biodistribution and pharmacokinetics of radiolabelled antibodies remain similar between dosimetric and therapeutic injections in radioimmunotherapy. However, circulation half-lives of unlabelled rituximab have been reported to increase progressively after the weekly injections of standard therapy doses. The aim of this study was to evaluate the evolution of the pharmacokinetics of repeated {sup 131}I-rituximab injections during treatment with unlabelled rituximab in patients with non-Hodgkin's lymphoma (NHL). Patients received standard weekly therapy with rituximab (375 mg/m{sup 2}) for 4 weeks and a fifth injection at 7 or 8 weeks. Each patient had three additional injections of 185 MBq {sup 131}I-rituximab in either treatment weeks 1, 3 and 7 (two patients) or weeks 2, 4 and 8 (two patients). The 12 radiolabelled antibody injections were followed by three whole-body (WB) scintigraphic studies during 1 week and blood sampling on the same occasions. Additional WB scans were performed after 2 and 4 weeks post {sup 131}I-rituximab injection prior to the second and third injections, respectively. A single exponential radioactivity decrease for WB, liver, spleen, kidneys and heart was observed. Biodistribution and half-lives were patient specific, and without significant change after the second or third injection compared with the first one. Blood T{sub 1/2}{beta}, calculated from the sequential blood samples and fitted to a bi-exponential curve, was similar to the T{sub 1/2} of heart and liver but shorter than that of WB and kidneys. Effective radiation dose calculated from attenuation-corrected WB scans and blood using Mirdose3.1 was 0.53+0.05 mSv/MBq (range 0.48-0.59 mSv/MBq). Radiation dose was highest for spleen and kidneys, followed by heart and liver. These results show that the biodistribution and tissue kinetics of {sup 131}I-rituximab, while specific to each patient, remained constant during unlabelled antibody therapy

  6. A multicenter randomized open-label study of rituximab plus rhTPO vs rituximab in corticosteroid-resistant or relapsed ITP.

    Science.gov (United States)

    Zhou, Hai; Xu, Miao; Qin, Ping; Zhang, Hai-yan; Yuan, Cheng-lu; Zhao, Hong-guo; Cui, Zhong-guang; Meng, Yue-sheng; Wang, Lei; Zhou, Fang; Wang, Xin; Li, Da-qi; Bi, Ke-hong; Zhu, Chuan-sheng; Guo, Cheng-shan; Chu, Xiao-xia; Wu, Qing-chao; Liu, Xin-guang; Dong, Xiao-yuan; Li, Jie; Peng, Jun; Hou, Ming

    2015-03-05

    This study aimed to compare the efficacy and safety of rituximab (RTX) plus recombinant human thrombopoietin (rhTPO) with RTX alone in patients with immune thrombocytopenia (ITP) who had failed to respond to corticosteroids or relapsed. Recruited patients were randomized at a ratio of 2:1 into 2 groups: the combination group (RTX + rhTPO, n = 77) and the monotherapy group (RTX, n = 38). Overall response was achieved in 79.2% of patients in the combination group vs 71.1% in the monotherapy group (P = .36), and the complete response (CR) rate was 45.4% in the combination group compared with 23.7% in the monotherapy group (P = .026). The combination group had significantly shorter time to response (TTR; median and range, 7 and 4-28 days) compared with the monotherapy group (28 and 4-90 days) (P rhTPO significantly increased the CR rate and shortened TTR compared with RTX monotherapy in the treatment of corticosteroid-resistant or relapsed ITP but failed to show a beneficial effect on the long-lasting response. This study is registered at www.clinicaltrials.gov as #NCT01525836.

  7. Methodology for management of therapeutic dose of I-131; Metodologia para administrar dosis terapeutica de I-131

    Energy Technology Data Exchange (ETDEWEB)

    Basteris M, J.; Gomez D, R. [Universidad Autonoma de Yucatan, Facultad de Medicina, Merida, Yucatan (Mexico)

    2007-07-01

    The present work suggests the use of measures guided to eliminate the resulting chronic sialoadenitis of the treatment previously described with a therapeutic dose bigger than ablative of Iodine 131, as well as the use of citric fruits to stimulate the salivation, the administration of liquid post-dose is included to accelerate the gastric emptying avoiding the secondary effects as the vomit. (Author)

  8. Mutational profile and prognostic significance of TP53 in diffuse large B-cell lymphoma patients treated with rituximab-CHOP

    DEFF Research Database (Denmark)

    Xu-Monette, Zijun Y; Wu, Lin; Visco, Carlo;

    2012-01-01

    TP53 mutation is an independent marker of poor prognosis in patients with diffuse large B-cell lymphoma (DLBCL) treated with cyclophosphamide, hydroxydaunorubicin, vincristine, and prednisone (CHOP) therapy. However, its prognostic value in the rituximab immunochemotherapy era remains undefined. ...

  9. 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...... therapy and with previous response to a rituximab-containing regimen were randomly assigned (1:1) to four once-per-week infusions of either obinutuzumab (1,000 mg) or rituximab (375 mg/m(2)). Patients without evidence of disease progression after induction therapy received obinutuzumab or rituximab...... 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...

  10. The efficacy and safety of rituximab in treatment of Epstein-Barr virus disease post allogeneic hematopoietic stem-cell transplantation

    Institute of Scientific and Technical Information of China (English)

    许兰平

    2013-01-01

    Objective To investigate the efficacy and safety of rituximab on Epstein-Barr virus(EBV) disease post allogeneic hematopoietic stem-cell transplantation. Methods A retrospective analysis was performed based on clinical

  11. 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 C;

    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......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...

  12. The risk of CNS involvement in aggressive lymphomas in the rituximab era.

    Science.gov (United States)

    Benevolo, Giulia; Chiappella, Annalisa; Vitolo, Umberto

    2013-12-01

    The risk of CNS dissemination and CNS prophylaxis strategies in aggressive non-Hodgkin lymphoma (NHL) is still debated. CNS dissemination is a rare but fatal event. A CNS prophylaxis is common for Burkitt and B-cell lymphoblastic lymphoma; however, in other NHLs, prophylactic treatments are not systematically warranted. Current risk models showed low sensitivity in predicting CNS involvement, implying overtreatment in roughly 70% of high-risk patients. Risk models in the rituximab era were modulated for the detection of occult CNS disease at diagnosis using flow cytometry. The optimal regimen for CNS prophylaxis in aggressive lymphoma patients has not been established thus far and should be modulated at different levels of 'intensity' such as standard intrathecal chemotherapy, 'active' intrathecal chemotherapy with liposomal cytarabine or more aggressive systemic treatment with high doses of drugs having good CNS bioavailability reserved for patients who are truly at high risk of CNS dissemination.

  13. Childhood immune thrombocytopenia: role of rituximab, recombinant thrombopoietin, and other new therapeutics.

    Science.gov (United States)

    Journeycake, Janna M

    2012-01-01

    Childhood immune thrombocytopenia (ITP) is often considered a benign hematologic disorder. However, 30% of affected children will have a prolonged course and 5%-10% will develop chronic severe refractory disease. Until recently, the only proven therapeutic option for chronic severe ITP was splenectomy, but newer alternatives are now being studied. However, because immunosuppressive agents such as rituximab are not approved for use in ITP and the thrombopoietin receptor agonists are not yet approved in children, the decision to use alternatives to splenectomy needs to be considered carefully. This review describes the factors that should affect decisions to treat ITP at diagnosis and compares the options for the occasional child in whom ITP does not resolve within the first year.

  14. Fatal Cytomegalovirus Disease after Combination Therapy with Corticosteroids and Rituximab for Granulomatosis with Polyangiitis

    Directory of Open Access Journals (Sweden)

    Talal Hilal

    2015-01-01

    Full Text Available The association of cytomegalovirus (CMV with autoimmune disease is poorly understood with suggested causality and reported viral reactivation coinciding with active inflammation. We report a case of a patient who presented with diffuse alveolar hemorrhage and acute renal failure from rapidly progressive glomerulonephritis ultimately diagnosed with granulomatosis with polyangiitis (GPA. She was acutely managed with plasmapheresis to reduce antibody-mediated end-organ damage, hemodialysis for worsening hyperkalemia and acidosis, and high-dose intravenous methylprednisolone. She was transitioned to oral prednisone and started on weekly rituximab with resultant remission induction over a three-week period at which point she developed reactivation of CMV causing severe fatal lung disease and viremia. The case highlights the multiple factors associated with CMV reactivation in cases of severe systemic inflammatory states and the need for further research to help establish practice guidelines regarding antimicrobial prophylaxis in patients with autoimmune diseases on prolonged courses of corticosteroids and biologic agents.

  15. Effective treatment with rituximab for the maintenance of remission in frequently relapsing minimal change disease

    Science.gov (United States)

    Shendi, Ali M.; Salama, Alan D.; Khosravi, Maryam; Connolly, John O.; Trompeter, Richard

    2016-01-01

    Abstract Aim Treatment of frequently relapsing or steroid‐dependent minimal change disease (MCD) in children and adults remains challenging. Glucocorticoids and/or other immunosuppressive agents are the mainstay of treatment, but patients often experience toxicity from prolonged exposure and may either become treatment dependent and/or resistant. Increasing evidence suggests that rituximab (RTX) can be a useful alternative to standard immunosuppression and allow withdrawal of maintenance immunosuppressants; however, data on optimal treatment regimens, long‐term efficacy and safety are still limited. Methods We undertook a prospective study of RTX to allow immunosuppression minimization in 15 young adults with frequently relapsing or steroid‐dependent, biopsy‐proven MCD. All patients were in remission at the start of treatment and on a calcineurin inhibitor. Two doses of RTX (1 gr) were given 6 months apart. A subset of patients also received an additional dose 12 months later, in order to examine the benefit of re‐treatment. Biochemical and clinical parameters were monitored over an extended follow‐up period of up to 43 months. Results Median steroid‐free survival after RTX was 25 months (range 4–34). Mean relapse frequency decreased from 2.60 ± 0.28 to 0.4 ± 0.19 (P < 0.001) after RTX. Seven relapses occurred, five of which (71%) when CD19 counts were greater than 100 µ. Immunoglobulin levels remained unchanged, and no major side effects were observed throughout the follow‐up period. Conclusions Rituximab therapy is effective at maintaining prolonged steroid‐free remission and reducing relapse frequency in this group of patients. Our study lends further support for the role of RTX in the treatment of patients with frequently relapsing or steroid‐dependent MCD. PMID:26860320

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

    Science.gov (United States)

    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.

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

    Energy Technology Data Exchange (ETDEWEB)

    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.)

  18. Endogenous neurotrophins and Trk signaling in diffuse large B cell lymphoma cell lines are involved in sensitivity to rituximab-induced apoptosis.

    Directory of Open Access Journals (Sweden)

    Cynthia Bellanger

    Full Text Available BACKGROUND: Diffuse large B-cell lymphoma (DLBCL is a common and often fatal malignancy. Immunochemotherapy, a combination of rituximab to standard chemotherapy, has resulted in improved survival. However a substantial proportion of patients still fail to reach sustained remission. We have previously demonstrated that autocrine brain-derived neurotrophic factor (BDNF production plays a function in human B cell survival, at least partly via sortilin expression. As neurotrophin receptor (Trks signaling involved activation of survival pathways that are inhibited by rituximab, we speculated that neurotrophins may provide additional support for tumour cell survival and therapeutic resistance in DLBCL. METHODOLOGY/PRINCIPAL FINDINGS: In the present study, we used two DLBCL cell lines, SUDHL4 and SUDHL6, known to be respectively less and more sensitive to rituximab. We found by RT-PCR, western blotting, cytometry and confocal microscopy that both cell lines expressed, in normal culture conditions, BDNF and to a lesser extent NGF, as well as truncated TrkB and p75(NTR/sortilin death neurotrophin receptors. Furthermore, BDNF secretion was detected in cell supernatants. NGF and BDNF production and Trk receptor expression, including TrkA, are regulated by apoptotic conditions (serum deprivation or rituximab exposure. Indeed, we show for the first time that rituximab exposure of DLBCL cell lines induces NGF secretion and that differences in rituximab sensitivity are associated with differential expression patterns of neurotrophins and their receptors (TrkA. Finally, these cells are sensitive to the Trk-inhibitor, K252a, as shown by the induction of apoptosis. Furthermore, K252a exhibits additive cytotoxic effects with rituximab. CONCLUSIONS/SIGNIFICANCE: Collectively, these data strongly suggest that a neurotrophin axis, such NGF/TrkA pathway, may contribute to malignant cell survival and rituximab resistance in DLBCL.

  19. Overcoming rituximab drug-resistance by the genetically engineered anti-CD20-hIFN-α fusion protein: Direct cytotoxicity and synergy with chemotherapy

    Science.gov (United States)

    VEGA, GABRIEL G.; FRANCO-CEA, LUZ ARELI; HUERTA-YEPEZ, SARA; MAYANI, HÉCTOR; MORRISON, SHERIE L.; BONAVIDA, BENJAMIN; VEGA, MARIO I.

    2015-01-01

    Treatment of patients with B-NHL with rituximab and CHOP has resulted in significant clinical responses. However, a subset of patients develops resistance to further treatments. The mechanism of unresponsiveness in vivo is not known. We have reported the development of rituximab-resistant clones derived from B-NHL cell lines as models to investigate the mechanism of resistance. The resistant clones exhibit hyper-activated survival/anti-apoptotic pathways and no longer respond to a combination of rituximab and drugs. Recent studies reported the therapeutic efficacy in mice bearing B-cell lymphoma xenografts following treatment with the anti-CD20-hIFNα fusion protein. We hypothesized that the fusion protein may bypass rituximab resistance and inhibit survival signaling pathways. Treatment of the rituximab-resistant clones with anti-CD20-hIFNα, but not with rituximab, IFNα, or rituximab+IFNα resulted in significant inhibition of cell proliferation and induction of cell death. Treatment with anti-CD20-hIFNα sensitized the cells to apoptosis by CDDP, doxorubicin and Treanda. Treatment with anti-CD20-hIFNα inhibited the NF-κB and p38 MAPK activities and induced the activation of PKC-δ and Stat-1. These effects were corroborated by the use of the inhibitors SB203580 (p38 MAPK) and Rottlerin (PKC-δ). Treatment with SB203580 enhanced the sensitization of the resistant clone by anti-CD20-hIFNα to CDDP apoptosis. In contrast, treatment with Rotterin inhibited significantly the sensitization induced by anti-CD20-hIFNα. Overall, the findings demonstrate that treatment with anti-CD20-hIFNα reverses resistance of B-NHL. These findings suggest the potential application of anti-CD20-hIFNα in combination with drugs in patients unresponsive to rituximab-containing regimens. PMID:26398317

  20. Fludarabine, cyclophosphamide and rituximab plus granulocyte macrophage colony-stimulating factor as frontline treatment for patients with chronic lymphocytic leukemia.

    Science.gov (United States)

    Strati, Paolo; Ferrajoli, Alessandra; Lerner, Susan; O'Brien, Susan; Wierda, William; Keating, Michael J; Faderl, Stefan

    2014-04-01

    Fludarabine, cyclophosphamide and rituximab (FCR), the standard of care for the frontline treatment of patients with chronic lymphocytic leukemia (CLL), is associated with a high rate of neutropenia and infectious complications. Granulocyte macrophage colony-stimulating factor (GM-CSF) reduces myelosuppression and can potentiate rituximab activity. We conducted a clinical trial combining GM-CSF with FCR for frontline treatment of 60 patients with CLL. Eighty-six percent completed all six courses and 18% discontinued GM-CSF for toxicity: grade 3-4 neutropenia was observed in 30% of cycles, and severe infections in 16% of cases. The overall response rate was 100%. Both median event-free survival (EFS) and overall survival (OS) have not been reached. Longer EFS was associated with favorable cytogenetics. GM-CSF led to a lower frequency of infectious complications than in the historical FCR group, albeit similar EFS and OS.

  1. Rituximab-associated progressive multifocal leukoencephalopathy derived from non-Hodgkin lymphoma: neuropathological findings and results of mefloquine treatment.

    Science.gov (United States)

    Sano, Yasuteru; Nakano, Yuta; Omoto, Masatoshi; Takao, Masaki; Ikeda, Eiji; Oga, Atsunori; Nakamichi, Kazuo; Saijo, Masayuki; Maoka, Takashi; Sano, Hironori; Kawai, Motoharu; Kanda, Takashi

    2015-01-01

    A 66-year-old man with non-Hodgkin lymphoma (NHL) developed progressive multifocal leukoencephalopathy (PML) after undergoing chemotherapy including rituximab. Although the administration of mefloquine at a dose of 500 mg weekly temporarily led to a dramatic decrease in the copy number of JC Virus DNA in the cerebrospinal fluid, the patient's symptoms gradually worsened. The CD4(+) T count remained continuously low, at least until approximately five months after the last cycle of chemotherapy. A postmortem examination performed 10 months after the onset of PML disclosed a severe condition associated with rituximab-treated PML originating from NHL and a high mefloquine concentration in the brain. The accumulation of further data regarding mefloquine treatment in PML cases may help to elucidate the optimal dosage and time window for effectively treating PML.

  2. Progressive Multifocal Leukoencephalopathy in a HIV-Negative Patient with Small Lymphocytic Leukemia following Treatment with Rituximab

    Directory of Open Access Journals (Sweden)

    Subhankar Chakraborty

    2011-03-01

    Full Text Available We describe a case of progressive multifocal leukoencephalopathy (PML caused by infection with the human polyomavirus JC virus in a patient with B-cell small lymphocytic leukemia who was treated with rituximab. The first symptoms of PML appeared immediately following the last of five cycles of rituximab, cyclophosphamide and pentostatin. Magnetic resonance imaging revealed changes consistent with PML, although JC virus DNA was not detected by polymerase chain reaction assay of the cerebrospinal fluid. A stereotactic biopsy of the brain showed histological changes consistent with PML, while electron microscopy revealed JC virus particles attached to the nuclei of astrocytes. The patient was treated supportively but died 53 days after the initial onset of symptoms.

  3. Unexpected and persistent depletion of B lymphocytes CD20 following a minimum dose of anti-CD20 antibody (Rituximab

    Directory of Open Access Journals (Sweden)

    V. Bruzzese

    2011-06-01

    Full Text Available Rituximab is a chemeric murine/human anti-B lymphocyte antigen CD20 monoclonal antibody used in the treatment of rheumatoid arthritis resistant to treatment by one or more anti TNF-alpha therapies (1. The recommended dose for an efficient depletion of the B CD 20 lymphocytes in rheumatoid arthritis is two infusions of 1000 mg, with the second infusion being administered two weeks after the first. At this dose, one obtains a rapid and persistent depletion of CD 20 cells, with repopulation occurring, on the average, in about eight months (2. Here, we present a case of a woman treated with only 50 mg of rituximab, who underwent both a rapid and pronounced reduction of B CD 20 lymphocytes...

  4. Refractory heparin induced thrombocytopenia with thrombosis (HITT) treated with therapeutic plasma exchange and rituximab as adjuvant therapy.

    Science.gov (United States)

    Schell, Amy M; Petras, Melissa; Szczepiorkowski, Zbigniew M; Ornstein, Deborah L

    2013-10-01

    We report a case of refractory heparin-induced thrombocytopenia with thrombosis (HITT) with prolonged thrombocytopenia and multiple thrombotic complications that failed to improve despite aggressive treatment. A 60 year old female with a prior history of venous thromboembolism was admitted with an acute pulmonary embolism, and developed HITT after several days on heparin therapy. She suffered multiple complications including bilateral venous limb gangrene, acute renal failure, and refractory thrombocytopenia, leading us to use multimodality therapy including therapeutic plasma exchange (TPE) and rituximab immunosuppression. The patient had transient improvements in her thrombocytopenia with TPE, and rituximab was added in an attempt to reduce antibody production. She eventually required bilateral limb amputation, and only after removal of the gangrenous limbs did her platelet count show sustained improvement. We discuss the possible contribution of infection to her prolonged course.

  5. The CXCR4 antagonist plerixafor enhances the effect of rituximab in diffuse large B-cell lymphoma cell lines

    DEFF Research Database (Denmark)

    Reinholdt, Linn; Laursen, Maria Bach; Schmitz, Alexander;

    2016-01-01

    . Accordingly, the fraction of apoptotic/dead cells significantly increased following addition of plerixafor to rituximab treatment. Furthermore, exposure of DLBCL cells to plerixafor resulted in a significant decrease in CXCR4 fluorescence intensity. CONCLUSIONS: Based on our results, implying that the anti......BACKGROUND: Diffuse large B-cell lymphoma (DLBCL) is an aggressive disease with variable clinical outcome, accounting for at least 25-30 % of adult non-Hodgkin lymphomas. Approximately one third of DLBCL patients are not cured by the currently used treatment regimen, R-CHOP. Hence, new treatment......-proliferative/pro-apoptotic effect of rituximab on DLBCL cells can be synergistically enhanced by the CXCR4 antagonist plerixafor, addition of plerixafor to the R-CHOP regimen can be suggested to improve treatment outcome for DLBCL patients....

  6. Sustained clinical response to rituximab in a case of life-threatening overlap subepidermal autoimmune blistering disease.

    Science.gov (United States)

    Li, Yaohan; Foshee, J B; Sontheimer, Richard D

    2011-04-01

    The conventional treatment for the autoimmune bullous skin diseases is broad-spectrum immunosuppressive regimen typically combining systemic corticosteroids with adjuvant immunosuppressive therapeutic agents. Orphan diseases in the pemphigus, pemphigoid, and epidermolysis bullosa acquisita groups of clinical disorders are often clinically severe, requiring long-term treatment with such drugs or drug combinations. Rituximab, a chimeric recombinant monoclonal antibody targeting CD20(+) B cells, has recently been suggested to be effective in the treatment of pemphigus with relatively few adverse effects. The clinical value of rituximab in other immune-mediated blistering diseases has been less thoroughly examined. We report a case of a woman who presented initially with the Brunsting-Perry phenotype of cicatricial pemphigoid who subsequently developed severe generalized subepidermal blisters healing with scarring and milia formation thought to be clinically compatible with epidermolysis bullosa acquisita, although type VII collagen autoantibodies were never identified. Treatment with a number of conventional systemic agents was unsuccessful and complicated by methicillin-resistant Staphylococcus aureus-induced cutaneous ulcers and near-fatal gram-negative sepsis. This woman has enjoyed an 18-month complete clinical remission after a single inductive 4-week cycle of intravenous rituximab. This outcome supports the idea that systemic memory B-cell depletion with drugs such as rituximab should be considered for therapeutically refractory subepidermal autoimmune blistering diseases in addition to intraepidermal autoimmune blistering diseases. A potential role for the immunologic phenomenon of epitope spreading in the generation of overlapping features of autoimmune blistering diseases, and its contribution to therapeutic refractoriness ("hardening"), is discussed.

  7. KIR/HLA interactions negatively affect rituximab- but not GA101 (obinutuzumab)-induced antibody-dependent cellular cytotoxicity.

    Science.gov (United States)

    Terszowski, Grzegorz; Klein, Christian; Stern, Martin

    2014-06-15

    Ab-dependent cellular cytotoxicity (ADCC) mediated by NK cells is regulated by inhibitory killer cell Ig-like receptors (KIRs), which interact with target cell HLA class I. We analyzed how KIR/HLA interactions influence ADCC induced by rituximab and by GA101, a novel type II CD20 Ab glycoengineered for increased FcgRIII binding and ADCC capacity. We found that KIR/HLA interactions strongly and selectively inhibit rituximab-induced in vitro ADCC toward target cells expressing cognate HLA KIR ligands. NK cells of donors carrying all three ligands to inhibitory KIR showed weak activation and target cell depletion capacity when incubated with rituximab and KIR-ligand matched target B cells. In contrast, NK cells from individuals missing one or more KIR ligands activated more strongly and depleted KIR ligand-matched target B cells more efficiently in the presence of rituximab. NK cells expressing a KIR for which the ligand was absent were the main effectors of ADCC in these donors. Notably, the influence of KIR/HLA interactions on NK cell activation was synergistic with the effect of the V158F FCGR3A single nucleotide polymorphism. In contrast, GA101 induced activation of NK cells irrespective of inhibitory KIR expression, and efficiency of target cell depletion was not negatively affected by KIR/HLA interactions. These data show that modification of the Fc fragment to enhance ADCC can be an effective strategy to augment the efficacy of therapeutic mAbs by recruiting NK cells irrespective of their inhibitory KIR expression.

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

    Directory of Open Access Journals (Sweden)

    Vanderlea Poeys Cabral

    Full Text Available ABSTRACT 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.

  9. Rituximab Treatment Strategy for Patients with Diffuse Large B-Cell Lymphoma after First-Line Therapy: A Systematic Review and Meta-Analysis

    Directory of Open Access Journals (Sweden)

    Yuan-Rong Ren

    2015-01-01

    Full Text Available Background: Rituximab in combination with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP significantly prolonged event-free survival in first-line chemotherapy for patients with diffuse large B-cell lymphoma (DLBCL. But relapse and refractory DLBCL occur frequently. Although rituximab is effective, its role in salvage therapy after autologous transplant remains unclear. Maintenance therapy with rituximab in responding patients after first line chemotherapy may be a useful novel approach capable of eradicating minimal residual disease and to bring survival benefit. This systematic review and meta-analysis evaluated the effects of rituximab maintenance treatment and salvage therapy of patients with DLBCL. Methods: We performed a systematic review and meta-analysis of randomized controlled trials and compared rituximab maintenance or salvage therapy at relapse with observation. We searched the Cochrane Library, PubMed, EMBASE, conference proceedings, databases of ongoing trials, and references of published trials. Two reviewers independently assessed the quality of the trials and extracted data. Hazard ratios for time-to-event data were estimated and pooled. Results: Seven trials including 1470 DLBCL patients were included in this systematic review and meta-analysis. Patients treated with maintenance rituximab have better overall survival (OS and event-free survival (EFS than patients in the observation arm, but there was no statistical significance. Patients who received rituximab salvage therapy for relapse or refractory DLBCL have statistically significantly better OS [HR of death = 0.72, 95% CI (0.55-0.94, P = 0.02], progression-free survival (PFS [HR = 0.61, 95% CI (0.52-0.72, P < 0.05], odds ratio (OR [RR = 1.26, 95% CI (1.07-1.47, P = 0.004] than patients in the observation arm. The rate of infection-related adverse events was higher with rituximab treatment [RR = 1.37, 95% CI = (1.14 - 1.65 P =0.001]. Conclusions: After

  10. Clinical experience with lenalidomide alone or in combination with rituximab in indolent B-cell and mantle cell lymphomas.

    Science.gov (United States)

    Ruan, J; Shah, B; Martin, P; Schuster, S J

    2016-07-01

    Lenalidomide is an oral immunomodulatory drug with significant activity in indolent B-cell and mantle cell lymphomas. Lenalidomide has a manageable safety profile whether administered as a single agent or in combination with rituximab. The combination of lenalidomide with rituximab, known as the 'R(2)' regimen, enhances efficacy over what has been shown with monotherapy and has demonstrated activity in patients considered resistant to rituximab. Tolerability of these regimens has been consistent among studies. Asymptomatic neutropenia is the most common grade 3/4 adverse event, typically managed by dose interruption, followed by dose reduction once neutrophils have recovered. Nonhematologic toxicities (e.g. fatigue) are generally low-grade, manageable with concomitant treatment, and/or lenalidomide dose modification. More frequent with R(2), immune-related symptoms such as rash and tumor flare are important to recognize as lenalidomide-associated treatment effects in patients with lymphoma who require supportive care and potential dose modifications. Severe tumor flare reactions with painful lymphadenopathy are not typically observed outside of chronic lymphocytic leukemia/small lymphocytic lymphoma. Venous thromboembolism is uncommon in lymphomas, though prophylaxis is recommended. The general safety profile, differences between lenalidomide monotherapy and R(2) treatment, and optimal strategies for managing adverse events are discussed here.

  11. Circulating miRNA-125b Is a Potential Biomarker Predicting Response to Rituximab in Rheumatoid Arthritis

    Directory of Open Access Journals (Sweden)

    Isabelle Duroux-Richard

    2014-01-01

    Full Text Available Although biologic therapies have changed the course of rheumatoid arthritis (RA, today’s major challenge remains to identify biomarkers to target treatments to selected patient groups. Circulating micro(miRNAs represent a novel class of molecular biomarkers whose expression is altered in RA. Our study aimed at quantifying miR-125b in blood and serum samples from RA patients, comparing healthy controls and patients with other forms of rheumatic diseases and arthritis, and evaluating its predictive value as biomarker for response to rituximab. Detectable levels of miR-125b were measured in total blood and serum samples and were significantly elevated in RA patients compared to osteoarthritic and healthy donors. The increase was however also found in patients with other forms of chronic inflammatory arthritis. Importantly, high serum levels of miR-125b at disease flare were associated with good clinical response to treatment with rituximab three months later (P=0.002. This predictive value was not limited to RA as it was also found in patients with B lymphomas. Our results identify circulating miR-125b as a novel miRNA over expressed in RA and suggest that serum level of miR-125b is potential predictive biomarker of response to rituximab treatment.

  12. Rituximab, fludarabine, and total body irradiation as conditioning regimen before allogeneic hematopoietic stem cell transplantation for advanced chronic lymphocytic leukemia: long-term prospective multicenter study.

    Science.gov (United States)

    Michallet, Mauricette; Socié, Gerard; Mohty, Mohamad; Sobh, Mohamad; Bay, Jacques-O; Morisset, Stéphane; Labussière-Wallet, Hélène; Tabrizi, Reza; Milpied, Noel; Bordigoni, Pierre; El-Cheikh, Jean; Blaise, Didier

    2013-02-01

    To evaluate the efficacy and toxicity of reduced-intensity conditioning (RIC) combining fludarabine, low-dose total body irradiation (TBI) and rituximab before allogeneic hematopoietic stem cell transplantation (allo-HSCT) from human leucocyte antigen (HLA) identical siblings, we conducted a prospective study in patients ≤65 years old with advanced chronic lymphocytic leukemia (CLL) stage B or C in response after a salvage treatment. Conditioning included rituximab (375 mg/m² on day 5), fludarabine (30 mg/m² from day 4 to day 2), TBI (2 Gy on day 0), and rituximab (500 mg/m² on days 1 and 8). Forty patients were included, 34 (85%) were male with a median age of 54 years (range, 35-65 years), 38 (95%) were in B stage, and 2 were in stage C; only 7 patients (17%) were in complete response. Seven (17%) patients did not receive rituximab. Thirty-nine (98%) patients engrafted, 17 patients developed acute graft-versus-host disease (GVHD) grade ≥II with a cumulative incidence at 3 months of 44% (36-52) with a significant protective effect of rituximab (p = 0.02). The cumulative incidence of chronic GVHD was 29% (21-36) at 12 months for both limited and extensive forms. The median overall survival was not reached with 5-years probability of 55% (41-74). The multivariate analysis showed a positive effect of rituximab on overall survival and event-free survival (hazard ratio [HR] = 0.1 [0-0.6], p = 0.02; and HR = 0.1 [0-0.4], p = 0.035, respectively). The association of fludarabine, TBI, and rituximab is feasible, well tolerated, and allows better outcomes in advanced CLL.

  13. 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

  14. Fcγ receptor IIIA polymorphisms and efficacy of rituximab therapy on Chinese diffuse large B-cell lymphoma

    Institute of Scientific and Technical Information of China (English)

    ZHANG Wei; WANG Xuan; Li Jian; DUAN Ming-hui; ZHOU Dao-bin

    2010-01-01

    Background Rituximab is used extensively in combination with chemotherapy to cure non-Hodgkin's lymphoma (NHL), and not only accelerates short-term improvement, but also prolongs patient survival and decreases relapse. The aim of this study was to evaluate the impact of Fcγ receptor IIIA (FcγRIIIA) gene polymorphisms on the response to rituximab therapy for newly diagnosed B-cell lymphomas. Methods Patients with newly diagnosed histologically-proven CD20-positive B-cell lymphoma were eligible for the study. All of the patients received rituximab combined with chemotherapy (CHOP). The FcγRIIIA type was analyzed by PCR. The initial efficacy was assessed after 6 cycles and the long-term survival was determined. Results Thirty-four patients were recruited between October 2005 and April 2006. The FcγRIIIA distribution was as follows: 11 patients were W, 5 were FF, and 18 were VF. After a median of 6 cycles (range 4-8) of rituximab combined chemotherapy, the overall response rate was 79% (82% in the VV group, 83% in the VF group, and 60% in the FF group; P=0.04). After a median follow-up time of 37 months (range 34-41), there were 12 relapses among 27 responders (44%); 5 of 9 patients (5/9) in the VV group, 5 of 15 patients (33%) in the VF group, and 2 of 3 patients (2/3) in the FF group (P=0.21). The 1-year overall survival in the VV, FF, and VF groups was 80%, 60%, and 80%, respectively, and the 3-year overall survival was 58%, 40%, and 69%, respectively (P=0.08). After analysis by COX regression, only the international prognosis index and response to initial treatment were significantly related to overall survival. Conclusions The distribution of FcγRIIIA polymorphisms in this B-cell lymphoma population shows that VF is most frequently expressed, followed by VV and FF. Patients with the FcγRIIIA VV and VF types are more sensitive to the initial treatment of rituximab combined with chemotherapy and have superior long-term survival compared with those with FF

  15. Rituximab Treatment Strategy for Patients with Diffuse Large B-Cell Lymphoma after First-Line Therapy: A Systematic Review and Meta-Analysis

    Institute of Scientific and Technical Information of China (English)

    Yuan-Rong Ren; Yong-Dong Jin; Zhi-Hui Zhang; Li Li; Ping Wu

    2015-01-01

    Background:Rituximab in combination with cyclophosphamide,doxorubicin,vincristine,and prednisone (CHOP) significantly prolonged event-free survival in first-line chemotherapy for patients with diffuse large B-cell lymphoma (DLBCL).But relapse and refractory DLBCL occur frequently.Although rituximab is effective,its role in salvage therapy after autologous transplant remains unclear.Maintenance therapy with rituximab in responding patients after first line chemotherapy may be a useful novel approach capable of eradicating minimal residual disease and to bring survival benefit.This systematic review and meta-analysis evaluated the effects of rituximab maintenance treatment and salvage therapy of patients with DLBCL.Methods:We performed a systematic review and meta-analysis of randomized controlled trials and compared rituximab maintenance or salvage therapy at relapse with observation.We searched the Cochrane Library,PubMed,EMBASE,conference proceedings,databases of ongoing trials,and references of published trials.Two reviewers independently assessed the quality of the trials and extracted data.Hazard ratios for time-to-event data were estimated and pooled.Results:Seven trials including 1470 DLBCL patients were included in this systematic review and meta-analysis.Patients treated with maintenance rituximab have better overall survival (OS) and event-free survival (EFS) than patients in the observation arm,but there was no statistical significance.Patients who received rituximab salvage therapy for relapse or refractory DLBCL have statistically significantly better OS [HR of death =0.72,95% CI (0.55-0.94),P=0.02],progression-free survival (PFS) [HR =0.61,95% CI (0.52-0.72),P< 0.05],odds ratio (OR) [RR =1.26,95% CI (1.07-1.47),P =0.004] than patients in the observation arm.The rate of infection-related adverse events was higher with rituximab treatment [RR =1.37,95% CI =(1.14-1.65) P =0.001].Conclusions:After first-line chemotherapy,the two rituximab

  16. Assessment of long-term radiotoxicity after treatment with the low-dose-rate alpha-particle-emitting radioimmunoconjugate {sup 227}Th-rituximab

    Energy Technology Data Exchange (ETDEWEB)

    Dahle, Jostein; Heyerdahl, Helen; Hjelmerud, Anne Kristine; Larsen, Roy H. [Oslo University Hospital, Department of Radiation Biology, The Norwegian Radium Hospital, Oslo (Norway); Jonasdottir, Thora J. [Norwegian School of Veterinary Science, Small Animal Section, Department of Companion Animal Clinical Sciences, Oslo (Norway); Nesland, Jahn M. [Oslo University Hospital, Division of Pathology, The Norwegian Radium Hospital, Oslo (Norway); University of Oslo, Faculty Division The Norwegian Radium Hospital, Medical Faculty, Oslo (Norway); Borrebaek, Joergen [Algeta AS, Oslo (Norway)

    2010-01-15

    The anti-CD20 antibody rituximab labelled with the {alpha}-particle-emitting radionuclide {sup 227}Th is of interest as a radiotherapeutic agent for treatment of lymphoma. Complete regression of human lymphoma Raji xenografts in 60% of mice treated with 200 kBq/kg {sup 227}Th-rituximab has been observed. To evaluate possible late side effects of {sup 227}Th-rituximab, the long-term radiotoxicity of this potential radiopharmaceutical was investigated. BALB/c mice were injected with saline, cold rituximab or 50, 200 or 1,000 kBq/kg {sup 227}Th-rituximab and followed for up to 1 year. In addition, nude mice with Raji xenografts treated with various doses of {sup 227}Th-rituximab were also included in the study. Toxicity was evaluated by measurements of mouse body weight, white blood cell (WBC) and platelet counts, serum clinical chemistry parameters and histological examination of tissues. Only the 1,000 kBq/kg dosage resulted in decreased body weight of the BALB/c mice. There was a significant but temporary decrease in WBC and platelet count in mice treated with 400 and 1,000 kBq/kg {sup 227}Th-rituximab. Therefore, the no-observed-adverse-effect level (NOAEL) was 200 kBq/kg. The maximum tolerated activity was between 600 and 1,000 kBq/kg. No significant signs of toxicity were observed in histological sections in any examined tissue. There were significantly (p < 0.05), but transiently, higher concentrations of serum bile acids and aspartate aminotransferase in mice treated with either {sup 227}Th-rituximab or non-labelled antibody when compared with control mice. The maximum tolerated dose to bone marrow was between 2.1 and 3.5 Gy. Therapeutically relevant dose levels of {sup 227}Th-rituximab were well tolerated in mice. Bone marrow suppression, as indicated by decrease in WBC count, was the dose-limiting radiotoxicity. These toxicity data together with anti-tumour activity data in a CD20-positive xenograft mouse model indicate that therapeutic effects could be

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

    Science.gov (United States)

    Rydén-Aulin, Monica; Boumpas, Dimitrios; Bultink, Irene; Callejas Rubio, Jose Luis; Caminal-Montero, Luis; Castro, Antoni; Colodro Ruiz, Agustín; Doria, Andrea; Dörner, Thomas; Gonzalez-Echavarri, Cristina; Gremese, Elisa; Houssiau, Frederic A; Huizinga, Tom; Inanç, Murat; Isenberg, David; Iuliano, Annamaria; Jacobsen, Søren; Jimenéz-Alonso, Juan; Kovács, Lászlo; Mariette, Xavier; Mosca, Marta; Nived, Ola; Oristrell, Joaquim; Ramos-Casals, Manuel; Rascón, Javier; Sáez-Comet, Luis; Salvador Cervelló, Gonzalo; Sebastiani, Gian Domenico; Squatrito, Danilo; Szücs, Gabriella; Voskuyl, Alexandre; van Vollenhoven, Ronald

    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 Data on patients with SLE receiving RTX were taken from the International Registry for Biologics in SLE retrospective registry and complemented with data on patients with SLE treated with conventional therapy. For nationwide estimates of RTX use in patients with SLE, investigators were asked to provide data through case report forms (CRFs). Countries for which no data were submitted through CRFs, published literature and/or personal communication were used, and for European countries where no data were available, estimates were made on the assumption of similarities with neighbouring countries. Results The estimated off-label use of RTX in Europe was 0.5%–1.5% of all patients with SLE. In comparison with patients with SLE on conventional therapy, patients treated with RTX had longer disease duration, higher disease activity and were more often treated with immunosuppressives. The most frequent 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 in Europe is restrictive and appears to be used as a last resort in patients for whom other reasonable options have been exhausted. PMID:27651920

  18. Immune tolerance induced using plasma exchange and rituximab in an infantile Pompe disease patient.

    Science.gov (United States)

    Deodato, Federica; Ginocchio, Virginia Maria; Onofri, Alfredo; Grutter, Giorgia; Germani, Alessandro; Dionisi-Vici, Carlo

    2014-06-01

    Infantile Pompe disease, resulting from deficiency of lysosomal acid α-glucosidase, requires enzyme replacement therapy with recombinant human acid α-glucosidase. Most patients develop antirecombinant human acid α-glucosidase antibodies, leading to reduced response to enzyme therapy in a subgroup of them. Aiming to improve treatment response, several immune tolerance induction strategies have been explored. We describe a patient with life-threatening infusion-associated reactions presenting anti-recombinant human acid α-glucosidase antibodies. He was successfully treated with an immune tolerance induction protocol, consisting of plasma exchange combined with a single dose of rituximab. Immediate reduction of antibody titer was obtained and enzyme therapy was resumed without infusion-associated reactions. Twenty-two months later, immunoglobulin G titer remained below 1:100. In conclusion, we applied a short-course immune tolerance induction strategy in a patient with severe infusion-associated reactions and anti-recombinant human acid α-glucosidase antibodies, leading to early and persisting reduction of antibody titer, in the absence of significant adverse events.

  19. Frontline chemoimmunotherapy with fludarabine, cyclophosphamide, alemtuzumab, and rituximab for high-risk chronic lymphocytic leukemia

    Science.gov (United States)

    Parikh, Sameer A.; Keating, Michael J.; O'Brien, Susan; Wang, Xuemei; Ferrajoli, Alessandra; Faderl, Stefan; Burger, Jan; Koller, Charles; Estrov, Zeev; Badoux, Xavier; Lerner, Susan

    2011-01-01

    Frontline chemoimmunotherapy with fludarabine, cyclophosphamide, and rituximab (FCR) is associated with superior overall survival (OS) for patients with chronic lymphocytic leukemia (CLL). Alemtuzumab (A) was added to FCR (CFAR) in a phase 2 trial for high-risk untreated patients < 70 years with serum β-2 microglobulin (β2M) ≥ 4 mg/L. Sixty patients were enrolled; median age was 59 years (range, 42-69); 75% were male; median β2M was 5.1 mg/L (range, 4-11.6); and 51% were Rai III-IV. Complete remission (CR) was achieved in 70%, partial remission (PR) in 18%, nodular PR in 3%, for an overall response of 92%. Of 14 patients with 17p deletion, CR was achieved by 8 (57%). Of 57 BM samples evaluated by 3-color flow cytometry at the end of treatment, 41 (72%) were negative for residual disease. Grade 3-4 neutropenia and thrombocytopenia occurred with 33% and 13% courses, respectively. The median progression-free survival was 38 months and median OS was not reached. In conclusion, CFAR is an active frontline regimen for high-risk CLL. Response rates and survival are comparable with historic high-risk FCR-treated patients. CFAR may be a useful frontline regimen to achieve CR in patients with 17p deletion before allogeneic stem cell transplantation. PMID:21750315

  20. Anti-tumor activity of obinutuzumab and rituximab in a follicular lymphoma 3D model.

    Science.gov (United States)

    Decaup, E; Jean, C; Laurent, C; Gravelle, P; Fruchon, S; Capilla, F; Marrot, A; Al Saati, T; Frenois, F-X; Laurent, G; Klein, C; Varoqueaux, N; Savina, A; Fournié, J-J; Bezombes, C

    2013-08-09

    Follicular lymphomas (FLs) account for 35-40% of all adult lymphomas. Treatment typically involves chemotherapy combined with the anti-CD20 monoclonal antibody (MAb) rituximab (RTX). The development of the type II anti-CD20 MAb obinutuzumab (GA101) aims to further improve treatment. Here, using FL cells we show that RTX and GA101 display a similar activity on RL cells cultured in 2D. However, 2D culture cannot mimic tumor spatial organization and conventional 2D models may not reflect the effects of antibodies as they occur in vivo. Thus, we created a non-Hodgkin's lymphoma (NHL) 3D culture system, termed multicellular aggregates of lymphoma cells (MALC), and used it to compare RTX and GA101 activity. Our results show that both antibodies display greater activity towards FL cells in 3D culture compared with 2D culture. Moreover, we observed that in the 3D model GA101 was more effective than RTX both in inhibiting MALC growth through induction of (lysosomal) cell death and senescence and in inhibiting intracellular signaling pathways, such as mammalian target of rapamycin, Akt, PLCgamma (Phospholipase C gamma) and Syk. Altogether, our study demonstrates that spatial organization strongly influences the response to antibody treatment, supporting the use of 3D models for the testing of therapeutic agents in NHL.

  1. 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.

  2. Fludarabine, cyclophosphamide, and rituximab in salvage therapy of Waldenström's macroglobulinemia.

    Science.gov (United States)

    Tedeschi, Alessandra; Ricci, Francesca; Goldaniga, Maria Cecilia; Benevolo, Giulia; Varettoni, Marzia; Motta, Marina; Pioltelli, Pietro; Gini, Guido; Barate', Claudia; Luraschi, Annamaria; Vismara, Eleonora; Frustaci, Anna Maria; Nichelatti, Michele; Vitolo, Umberto; Baldini, Luca; Morra, Enrica

    2013-04-01

    The combination FCR (fludarabine, cyclophosphamide, and rituximab) proved to be active in Waldenström's macroglobulinemia in a mixed population of untreated and previously treated patients. Prolonged myelosuppression and concerns about purine analogue treatment led to the conclusion that this regimen should be avoided in younger patients in first-line treatment. In this retrospective study on 40 patients we observed a response rate of 80% (32) after FCR salvage treatment with 32.5% (13) of patients reaching at least a very good partial remission. None of the prognostic variables had a significant effect on response or good quality of response achievement. Median event-free survival was reached at 77 months; median progression-free survival was not reached after a median follow-up of 51 months with any difference when categorizing patients according to quality of response. The results of this study suggest that the FCR regimen might overcome poor prognostic features and should be taken into account as salvage treatment. Tardive immunosuppression and myelosuppression warrant accurate patient follow-up.

  3. [Rituximab (MabThera)--a new biological medicine in rheumatoid arthritis therapy].

    Science.gov (United States)

    Nemec, P

    2007-11-01

    Rheumatoid arthritis (RA) is a serious, chronic, inflammatory disorder that damages the joints. The chronic destructive process causes pain to patients with RA and leads to the development of permanent disability. At present, great emphasis is placed on timely and effective therapy for RA, which is able to halt or slow the development of the disorder. At present we do not have any means of curing RA, the main objective for treatment is to induce remission of the disorder and prevent structural damage to the joints and the development of permanent disability. The relatively frequent failure of disease modifying medications (DMARDs) lead to efforts to find new resources for the treatment of RA. So called biological medicines were recently introduced into therapeutic use. These were mainly TNFalpha blockers. Experience has shown that approximately a third of patients with RA do not respond even to treatment with such medicines. Rituximab (MabThera), a monoclonal antibody against CD20 positive B-lymphocytes, is a new biological medicine approved for RA therapy. It represents a new hope for patients with active RA, for whom earlier therapy with TNFa blockers has failed.

  4. Radioimmunotherapy with {sup 131}I-Rituximab in a Patient with Diffuse Large B-Cell Lymphoma Relapsed After Treatment with {sup 90}Y-Ibritumomab Tiuxetan

    Energy Technology Data Exchange (ETDEWEB)

    Kang, Geon Wook; Kang, Hye Jin; Shin, Dongyeop; Gu, Ha Ra; Choi, Hong Seok; Lim, Sang Moo [Korea Cancer Center Hospital, Seoul (Korea, Republic of)

    2013-12-15

    We report a case that demonstrates the efficacy of radioimmunotherapy (RIT) with radioiodinated rituximab ({sup 131}I-rituximab) for relapsed diffuse large B-cell lymphoma (DLBCL). A 79-year-old male patient with DLBCL initially achieved a complete response (CR) after six cycles of RCHOP (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone) therapy. However, the lymphoma relapsed 20 months later. Although the patient had achieved a second and a third CR after two cycles of {sup 90}Y-ibritumomab tiuxetan, he experienced a third relapse approximately 3 years later. Between March and June 2011, the patient received three cycles of {sup 131}I-rituximab. Although he had achieved partial response after the second cycle, the disease progressed after the third cycle, and the total progression. Free survival was thus 5 months. The patient suffered only relatively mild toxicity (grade 1 thrombocytopenia) during treatment. RIT with {sup 131}I-rituximab is therefore potentially effective in patients with relapsed DLBCL, even after the failure of {sup 90}Y-ibritumomab tiuxetan therapy.

  5. Effectiveness of disease-modifying antirheumatic drug co-therapy with methotrexate and leflunomide in rituximab-treated rheumatoid arthritis patients: results of a 1-year follow-up study from the CERERRA collaboration.

    NARCIS (Netherlands)

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

    2012-01-01

    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 patient

  6. Effectiveness of disease-modifying antirheumatic drug co-therapy with methotrexate and leflunomide in rituximab-treated rheumatoid arthritis patients : results of a 1-year follow-up study from the CERERRA collaboration

    NARCIS (Netherlands)

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

    2012-01-01

    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 w

  7. 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

    DEFF Research Database (Denmark)

    Chatzidionysiou, Katerina; Lie, Elisabeth; Nasonov, Evgeny;

    2011-01-01

    To assess the 6-month effectiveness of the first rituximab (RTX) course in rheumatoid arthritis (RA) and to identify possible predictors of response.......To assess the 6-month effectiveness of the first rituximab (RTX) course in rheumatoid arthritis (RA) and to identify possible predictors of response....

  8. Progressive multifocal leukoencephalopathy secondary to rituximab-induced immunosuppression and the presence of John Cunningham virus: a case report and literature review.

    Science.gov (United States)

    Kelly, Deirdre; Monaghan, Bernadette; McMahon, Eileen; Watson, Geoffrey; Kavanagh, Eoin; O'Rourke, Killian; McCaffrey, John; Carney, Desmond

    2016-09-01

    We present the case of a 60-year-old man who developed subacute neurologic changes, in the setting of stage III non-Hodgkin's follicular lymphoma, and was treated with induction chemotherapy, followed by a year of maintenance rituximab. Magnetic resonance imaging of the brain with gadolinium was pathognomonic for progressive multifocal leukoencephalopathy (PML). He was treated with sequential plasmapheresis and intravenous immunoglobulin with clinical improvement. A literature review of the diagnostic workup of rituximab-induced PML was undertaken. This case and the literature review demonstrate the important role of magnetic resonance imaging of the brain in diagnosis and follow-up of rituximab-induced PML. Specific radiologic features in combination with cerebrospinal fluid can be diagnostic and avoid the morbidity and mortality of a diagnostic brain biopsy. Plasmapheresis and intravenous immunoglobulin have a therapeutic role and demonstrate symptom improvement and disease control. Follow-up imaging in combination with clinical response is important in demonstrating a treatment response.

  9. Loss of CD20 expression in relapsed diffuse large B cell lymphoma after rituximab therapy: a case report and review of the literature

    Institute of Scientific and Technical Information of China (English)

    Yao Jiang; Yingchao Zhao; Xiaorong Dong; Sheng Zhang; Yan Li; Gang Wu

    2013-01-01

    Nowadays, resistance to rituximab has become a major issue in clinical practice. And loss of CD20 may contribute to it. Here we presented a case of loss of CD20 expression in relapsed diffuse large B cell lymphoma treated with rituximab and discuss the incidence, mechanism, influence factors, specific markers, prognosis and treatment of this disease. These results suggested that a post-relapse biopsy after rituximab treatment should be performed. CD79a and Pax-5 should be used as the first-line B lineage-specific markers for these patients. Though mechanisms of CD20 decrement are not fully elucidated, the down-regulation of CD20 mRNA is the most probable hypothesis. Recently various new agents are developed, but the prognosis is still poor. Further studies for new treatments are needed.

  10. 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.

  11. Cholestatic liver disease after rituximab and adalimumab and the possible role of cross-reacting antibodies to Fab 2 fragments.

    Directory of Open Access Journals (Sweden)

    Joerg Latus

    Full Text Available BACKGROUND: Millions of patients are treated with therapeutic monoclonal antibodies (Tmabs for miscellaneous diseases. We investigated sera from six patients who received immune globulin, from one patient with refractory anti-neutrophil-cytoplasmic antibody (ANCA-associated granulomatosis with polyangiitis (GPA who developed two episodes of acute cholestatic liver disease, one after treatment with rituximab and a second after adalimumab and a healthy control group. METHODS: Three sera from the patient and six sera from patients who received immune globulin were analyzed for antibodies to rituximab and adalimumab by ELISA. Additionally, sera from the patients and from nine healthy blood donors were coated with the Fab fragment of an unrelated humanized monoclonal antibody, with human Fc proteins as well as a mouse IgG globulin. RESULTS: Viral serology for hepatitis A, B, C and autoantibodies specific for autoimmune liver disorders were negative. In all three sera from the patient antibodies to rituximab could be detected, but also antibodies to adalimumab were present even at time points when the patient had not yet received adalimumab, indicating cross reactivity between both substances. Testing against an unrelated human Fab fragment revealed positive results, indicating that the patient had antibodies against human Fab fragments in general. The Fc proteins were negative, and patients' sera did also not react with mouse IgG globulins. Remarkably, 2 out of 5 patients which were treated with immune globulin had antibodies against human Fab fragments in general whereas in none of the samples from healthy controls antibodies to Fab fragment could be detected. CONCLUSION: This is the first study demonstrating cholestatic liver disease induced by two different Tmabs. Cross - reacting antibodies to Fab2 fragments in general are probably involved. Further studies must show if these Fab2 antibodies in general are related with drug-induced side effects

  12. A phase I-II trial of fludarabine, bendamustine and rituximab (FBR) in previously treated patients with CLL.

    Science.gov (United States)

    Jain, Nitin; Balakrishnan, Kumudha; Ferrajoli, Alessandra; O'Brien, Susan M; Burger, Jan A; Kadia, Tapan M; Cortes, Jorge E; Ayres, Mary L; Tambaro, Francesco Paolo; Keating, Michael J; Gandhi, Varsha; Wierda, William G

    2016-09-15

    Chemoimmunotherapy regimens have been the standard first-line therapy for patients with chronic lymphocytic leukemia (CLL). For young, fit patients the standard of care is combination of fludarabine, cyclophosphamide, and rituximab (FCR). Based on the preclinical work demonstrating that bendamustine combined with fludarabine resulted in increased DNA damage, we designed a phase I-II clinical trial with fludarabine, bendamustine, and rituximab (FBR) for patients with relapsed/refractory CLL. Treatment consisted of fludarabine 20 mg/m2 daily x 3 days and rituximab 375-500 mg/m2 x 1 day. Phase I included bendamustine at increasing doses of 20, 30, 40, or 50 mg/m2 daily x 3 days; phase II was with FR, and B at the selected dose. DNA damage response (H2AX phosphorylation) was evaluated in a subset of patients. Fifty-one patients were enrolled. The median age was 62 years; median number of prior therapies was 2; 40% had del(11q); and 41 patients had received prior FCR-based therapies. Hematologic toxicity was more common in ≥40 mg/m2 dose cohorts. Maximum tolerated dose (MTD) was not identified. Bendamustine-elicited H2AX phosphorylation was not dose-dependent, but markedly increased after fludarabine. We identified bendamustine 30 mg/m2 as the safe dose for phase II. The overall response rate (ORR) was 67% with 36% complete response (CR) / CR with incomplete count recovery (CRi). Younger patients (<65 years) had significantly higher ORR (81% vs. 50%; p=0.038). The median progression-free survival was 19 months, and the median overall survival was 52.5 months. FBR is an effective and tolerable CIT regimen for patients with relapsed CLL.

  13. Successful treatment of autoimmune and lymphoproliferative complications of patients with intrinsic B-cell immunodeficiencies with Rituximab.

    Science.gov (United States)

    Hennig, Christian; Baumann, Ulrich; Ilginus, Claudia; Horneff, Gerd; Foell, Juergen; Hansen, Gesine

    2010-02-01

    The heterogeneous group of primary immunodeficiencies requires personalized diagnosis and therapy to acheive an optimal outcome for each patient. This was exemplified by two patients with intrinsic B-cell class-switch defects (subclass of Hyper-IgM syndromes), where lymphoproliferation and autoimmunity determined the clinical course for many years due to lack of exact diagnosis. Based on genetics or a novel functional diagnostic approach, a definite individual diagnosis was established for each patient and they started Rituximab therapy. Autoimmune phenomena and generalized lymphadenopathy disappeared and remained well controlled during the observation period (3-4 years) without adverse effects. Quality of life increased remarkably in both patients.

  14. Salmonella Enteritidis Empyema Preceding the Diagnosis of Non-Hodgkin’s Lymphoma and Subsequent Contralateral Chylothorax Treated with Radiolabeled Rituximab

    Directory of Open Access Journals (Sweden)

    Syed Ali

    2015-12-01

    Full Text Available Salmonella infection is common, but pleural involvement has rarely been reported. Only seven cases of Salmonella enteritidis pleural empyema have been reported; all had an associated preexisting underlying immunosuppresion or malignancy. We report the case of an apparently healthy man who developed S. enteritidis empyema. On further follow-up and surveillance, he eventually presented with non-Hodgkin’s lymphoma and a contralateral recurrent chylothorax. The latter was successfully controlled with radiolabeled rituximab, which has never been described for the above purpose in literature before.

  15. 非霍奇金淋巴瘤的Rituximab治疗%Rituximab-the drug for non-Hodgkin's lymphoma

    Institute of Scientific and Technical Information of China (English)

    师明磊; 胡显文; 陈惠鹏

    2004-01-01

    Rituximab是用于治疗非霍奇金淋巴瘤(NHL)的单抗药物.Rituximab单独使用对B细胞NHL总有效率为40%~50%;和化疗药物联用有效率达90%以上.毒性作用轻微,是临床治疗B细胞NHL的安全有效的新药.现综述Rituximab用于治疗各种类型NHL的临床试验以及与其他药物联用的临床试验.

  16. Successful treatment of severe myasthenia gravis developed after allogeneic hematopoietic stem cell transplantation with plasma exchange and rituximab.

    Science.gov (United States)

    Unal, Sule; Sag, Erdal; Kuskonmaz, Baris; Kesici, Selman; Bayrakci, Benan; Ayvaz, Deniz C; Tezcan, Ilhan; Yalnızoglu, Dilek; Uckan, Duygu

    2014-05-01

    Myasthenia gravis is among the rare complications after allogeneic hematopoietic stem cell transplantation and is usually associated with chronic GVHD. Herein, we report a 2-year and 10 months of age female with Griscelli syndrome, who developed severe myasthenia gravis at post-transplant +22nd month and required respiratory support with mechanical ventilation. She was unresponsive to cyclosporine A, methylprednisolone, intravenous immunoglobulin, and mycophenolate mofetil and the symptoms could only be controlled after plasma exchange and subsequent use of rituximab, in addition to cyclosporine A and mycophenolate mofetil maintenance. She is currently asymptomatic on the 6th month of follow-up.

  17. Lenalidomide-bendamustine-rituximab in untreated mantle cell lymphoma > 65 years, the Nordic Lymphoma Group phase I+II trial NLG-MCL4

    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...

  18. Myelosuppression After Frontline Fludarabine, Cyclophosphamide, and Rituximab in Patients With Chronic Lymphocytic Leukemia

    Science.gov (United States)

    Strati, Paolo; Wierda, William; Burger, Jan; Ferrajoli, Alessandra; Tam, Constantine; Lerner, Susan; Keating, Michael J.; O’Brien, Susan

    2015-01-01

    BACKGROUND The combination of fludarabine, cyclophosphamide, and rituximab (FCR) has produced improved response rates and a prolonged survival in patients with chronic lymphocytic leukemia (CLL). However, its therapeutic power is counterbalanced by significant hematologic toxicity. Persistent and new-onset cytopenia after the completion of FCR raise concern about disease recurrence, the development of therapy-related myeloid malignancies (TRMM), and infections. METHODS A total of 207 patients with CLL who achieved complete response, complete response with incomplete bone marrow recovery, or nodular partial remission were analyzed after frontline FCR therapy. RESULTS Three months after the completion of therapy, 35% of patients had developed grade 2 to 4 cytopenia (according to Common Terminology Criteria for Adverse Events [version 4.0]). Factors found to be associated with cytopenia at 3 months after therapy were older age, advanced Rai stage disease, and lower baseline blood counts. Moreover, patients with cytopenia were less likely to have completed 6 courses of therapy with FCR. At 6 months and 9 months after therapy, the prevalence of grade 2 to 4 cytopenia was 24% and 12%, respectively. No differences in progression-free survival and overall survival were noted between cytopenic and noncytopenic patients or between patients with persistent and new-onset cytopenia. The prevalence of TRMM was 2.3% and did not differ significantly between cytopenic and noncytopenic patients or between those with persistent and new-onset disease. Late infections were more common in patients who were cytopenic at 9 months (38%) and were mostly bacterial (67%). CONCLUSIONS Cytopenia after the completion of therapy is a common complication of frontline FCR that improves over time, particularly for new-onset cases. The presence of persistent cytopenia (lasting up to 9 months after the completion of therapy) should not raise concern about CLL recurrence of the development of TRMM, but

  19. Rituximab in systemic lupus erythematosus: an updated systematic review and meta-analysis.

    Science.gov (United States)

    Duxbury, B; Combescure, C; Chizzolini, C

    2013-12-01

    The wide spectrum of clinical manifestations and high relapse rate represent a therapeutic challenge in systemic lupus erythematosus (SLE). Observational studies suggested efficacy of rituximab (RTX), a B-cell-targeting antibody, to control the activity of SLE. Two randomized trials controlled by placebo did not prove the superiority of RTX when used in addition to conventional treatment in nonrenal (EXPLORER) and renal (LUNAR) lupus. A systematic review of studies exploring the efficacy of RTX in SLE patients was conducted. The pooled percentages of response were assessed. Thirty studies with 1243 patients were analyzed. In studies using the British Isles Lupus Assessment Group (BILAG), the complete response (CR) rate was 46.7% (95% CI 36.8%-56.8%) and the partial response (PR) was 37.9% (95% CI 30.6%-45.8%). With the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI), the CR was 56.6% (95% CI 32.4%-78.1%) and the PR was 30.9% (95% CI 8.9%-46%). In renal lupus the CR was 36.1% (95% CI 25.2%-48.6%); PR was 37.4% (95% CI 28.5%-47.3%). In EXPLORER, CR was 12.4% and PR was 17.2%; in LUNAR CR was 26.4% and PR was 30.6%, in both cases not different from controls. Assessment and standardization of SLE response to treatment remain a challenge. The discrepancy in the perceived efficacy of RTX between controlled and observational studies reflects the heterogeneity of lupus and stringency in criteria of response. Further randomized trials focusing on selected SLE manifestations and using composite response indices are warranted.

  20. Protein A immunoadsorption combined with rituximab in highly sensitized kidney transplant recipients

    Institute of Scientific and Technical Information of China (English)

    YIN Hang; HU Xiao-peng; LI Xiao-bei; LIU Hang; WANG Wei; REN Liang; WANG Yong; ZHANG Xiao-dong

    2009-01-01

    Background The number of highly sensitized patients is rising, and sensitization can lead to renal transplant failure.The present study aimed to investigate the safety and efficacy of protein A immunoadsorption combined with rituximab (RTX) in highly sensitized recipients of kidney transplants.Methods Seven highly sensitized recipients of living-related renal transplants (4 men and 3 women, mean aged 42.5 years old (range 33-51)) were pretreated with this combination. Human leukocyte antigen (HLA) mismatch number was 2-5. Panel reactive antibody (PRA) of class 1 was high in 2 cases and that of class Ⅱ was high in 1 case. All patients were pretreated with immunoadsorption 2-10 times. Immunoglobulin and PRA changes were monitored before and after absorption. The operation was conducted when PRA or immunoglobulin levels were at or below normal levels.Immunosuppressive drugs were provided 3-5 days before the operation, and one dose of RTX (375 mg/m~2) was infused with polyclonal antibody on the day of operation. Postoperative creatinine (Cr), creatinine clearance rate (Ccr), PRA ratio,and immunoglobulin changes were monitored.Results All 7 patients had good recovery without delayed graft function. Acute rejection occurred in 3 cases at postoperative days 8, 10, and 14, respectively. The Banff 07 biopsy grades were la in 1 case and lla C4d0 in 2 cases.Successful reversion was achieved after giving methylprednisolone or antithymocyte immunoglobulin + cyclophosphamide. All patients were discharged with normal renal function, mean class 1 PRA was 14% and mean class Ⅱ PRA was 35%. PRA was completely negative in 3 cases.Conclusion Protein A immunoadsorption combined with RTX can safely reduce the occurrence of humoral rejection in highly sensitized renal transplant recipients.

  1. Low-dose rituximab in adult patients with idiopathic autoimmune hemolytic anemia: clinical efficacy and biologic studies.

    Science.gov (United States)

    Barcellini, Wilma; Zaja, Francesco; Zaninoni, Anna; Imperiali, Francesca Guia; Battista, Marta Lisa; Di Bona, Eros; Fattizzo, Bruno; Consonni, Dario; Cortelezzi, Agostino; Fanin, Renato; Zanella, Alberto

    2012-04-19

    This prospective study investigated the efficacy, safety, and response duration of low-dose rituximab (100 mg fixed dose for 4 weekly infusions) together with a short course of steroids as first- or second-line therapy in 23 patients with primary autoimmune hemolytic anemia (AIHA). The overall response was 82.6% at month +2, and subsequently stabilized to ∼ 90% at months +6 and +12; the response was better in warm autoimmune hemolytic anemia (WAIHA; overall response, 100% at all time points) than in cold hemagglutinin disease (CHD; average, 60%); the relapse-free survival was 100% for WAIHA at +6 and +12 months versus 89% and 59% in CHD, respectively, and the estimated relapse-free survival at 2 years was 81% and 40% for the warm and cold forms, respectively. The risk of relapse was higher in CHD and in patients with a longer interval between diagnosis and enrollment. Steroid administration was reduced both as cumulative dose (∼ 50%) and duration compared with the patient's past history. Treatment was well tolerated and no adverse events or infections were recorded; retreatment was also effective. The clinical response was correlated with amelioration biologic markers such as cytokine production (IFN-γ, IL-12, TNF-α, and IL-17), suggesting that low-dose rituximab exerts an immunomodulating activity. This study is registered at www.clinicaltrials.gov as NCT01345708.

  2. Rituximab in combination with high-dose methylprednisolone for the treatment of fludarabine refractory high-risk chronic lymphocytic leukemia

    Science.gov (United States)

    Castro, JE; Sandoval-Sus, JD; Bole, J; Rassenti, L; Kipps, TJ

    2017-01-01

    We examined the clinical response of fludarabine-refractory CLL patients treated with high-dose methylprednisolone (HDMP) and rituximab. Fourteen patients were treated with three cycles of rituximab (375mg/m2 weekly for 4 weeks) in combination with HDMP (1gm/m2 daily for 5 days). All patients were refractory to fludarabine and 86% had high-risk disease by the modified Rai classification. In all, 79% of the patients had CLL cells that expressed ZAP-70 and three patients had poor prognostic cytogenetics. The overall response rate was 93% and the complete remission rate was 36%. The median time-to-progression was 15 months and the median time-to-next treatment was 22 months. Median survival has not been reached after a median follow up of 40 months. Four patients have died of progressive disease. Patients tolerated the treatment well and serious adverse events were rare. This allowed patients to receive all planned treatments on schedule with no dose modifications. All but one patient responded to treatment and the overall survival and time-to-progression were superior to those of other published salvage regimens. PMID:18754025

  3. Glycoengineered CD20 antibody obinutuzumab activates neutrophils and mediates phagocytosis through CD16B more efficiently than rituximab.

    Science.gov (United States)

    Golay, Josée; Da Roit, Fabio; Bologna, Luca; Ferrara, Claudia; Leusen, Jeanette H; Rambaldi, Alessandro; Klein, Christian; Introna, Martino

    2013-11-14

    Obinutuzumab (GA101) is a glycoengineered type 2 CD20 antibody with enhanced CD16A-binding and natural killer-mediated cytotoxicity. CD16B is highly homologous to CD16A and a major FcγR on human polymorphonuclear neutrophils (PMNs). We show here that glycoengineered obinutuzumab or rituximab bound CD16B with approximately sevenfold higher affinity, compared with nonglycoengineered wild-type parental antibodies. Furthermore, glycoengineered obinutuzumab activated PMNs, either purified or in chronic lymphoblastic leukemia whole blood, more efficiently than wild-type rituximab. Activation resulted in a 50% increase in CD11b expression and 70% down-modulation of CD62L on neutrophils and in release of tumor necrosis factor alpha, IL-6, and IL-8. Activation was not accompanied by generation of reactive oxygen species or antibody-dependent cellular cytotoxicity activity, but led to up to 47% phagocytosis of glycoengineered anti-CD20 opsonized chronic lymphoblastic leukemia targets by purified PMNs. Significant phagocytosis was observed in whole blood, but only in the presence of glycoengineered antibodies, and was followed by up to 50% PMN death. Finally we show, using anti-CD16B and anti-CD32A Fab and F(ab')2 fragments, that both of these receptors are involved in PMN activation, phagocytosis, and cell death induced by glycoengineered antibodies. We conclude that phagocytosis by PMNs is an additional mechanism of action of obinutuzumab mediated through its higher binding affinity for CD16B.

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

    Energy Technology Data Exchange (ETDEWEB)

    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.)

  5. Targeted alpha therapy in vivo: direct evidence for single cancer cell kill using {sup 149}Tb-rituximab

    Energy Technology Data Exchange (ETDEWEB)

    Beyer, G.J.; Soloviev, D.; Buchegger, F. [Division of Nuclear Medicine, University Hospital of Geneva, 24 Rue Micheli du Crest, 1211, Geneva 14 (Switzerland); Miederer, M. [Department of Molecular Pharmacology and Chemistry, Memorial Sloan-Kettering Cancer Center, New York (United States); Vranjes-Duric, S. [Laboratory of Radioisotopes, Vinca Institute of Nuclear Sciences, Belgrade (Czechoslovakia); Comor, J.J. [Laboratory of Physics, Vinca Institute of Nuclear Sciences, Belgrade (Czechoslovakia); Kuenzi, G.; Hartley, O. [Department of Medical Biochemistry, University Medical Center, Geneva (Switzerland); Senekowitsch-Schmidtke, R. [Clinic of Nuclear Medicine, Technical University of Munich, Munich (Germany)

    2004-04-01

    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{sup 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 {mu}g 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 {sup 149}Tb is worthy of consideration as a new-generation radio-immunotherapeutic approach. (orig.)

  6. [Development of syndrome of inappropriate secretion of ADH and reversible posterior leukoencephalopathy during initial rituximab-CHOP therapy in a patient with diffuse large B-cell lymphoma].

    Science.gov (United States)

    Mizutani, Minoru; Nakamori, Yoshiki; Sakaguchi, Haruna; Kageyama, Yuki; Oya, Eiko; Ino, Kazuko; Suzuki, Kei; Sekine, Takao

    2013-03-01

    A 61-year-old woman presented with a right mandibular tumor and was diagnosed with DLBCL clinical stage IIIA from the biopsy results of the tumor and CT examination. An initial rituximab was administrated a week after the first CHOP treatment. During the infusion of rituximab, she exhibited disorientation, seizure, and consciousness disturbance. Hyponatremia due to SIADH and hypertension were coincidentally observed. MRI revealed T2 and FLAIR hyperintense signals involving the bilateral occipital, parietal, frontal lobes and the cerebellum that were consistent with reversible posterior leukoencephalopathy syndrome (RPLS). Her consciousness level recovered in parallel with corrections in serum sodium levels and blood pressure. Although she presented with transient cortical blindness, all neurological abnormalities disappeared 40 hours after the occurrence of seizure. She received a further 7 cycles of CHOP followed by 7 cycles of rituximab treatment with no relapse of RPLS. After irradiation for a residual abdominal tumor, she has maintained complete remission for 2 years. Although RPLS is a rare complication of rituximab-CHOP chemotherapy, it should be considered in patients with DLBCL who present with acute neurological deterioration.

  7. 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...

  8. Long-term durable remission by cladribine followed by rituximab in patients with hairy cell leukaemia: update of a phase II trial.

    Science.gov (United States)

    Chihara, Dai; Kantarjian, Hagop; O'Brien, Susan; Jorgensen, Jeffrey; Pierce, Sherry; Faderl, Stefan; Ferrajoli, Alessandra; Poku, Rebecca; Jain, Preetesh; Thompson, Phillip; Brandt, Mark; Luthra, Rajyalakshmi; Burger, Jan; Keating, Michael; Ravandi, Farhad

    2016-09-01

    Nucleoside analogues are highly active in patients with hairy cell leukaemia (HCL); however, patients continue to relapse. This phase II study evaluated the efficacy and safety of cladribine followed by rituximab in patients with untreated HCL (N = 59), relapsed HCL (N = 14) and HCL variant (HCLv, N = 7). Cladribine 5·6 mg/m(2) was given intravenously (IV) daily for 5 d and was followed approximately 1 month later with rituximab 375 mg/m(2) IV weekly for 8 weeks. Complete response rate in patients with untreated HCL, relapsed HCL and HCLv was 100%, 100% and 86%, respectively. With a median follow up of 60 months, 5-year failure-free survival (FFS) in patients with untreated HCL, relapsed HCL and HCLv was 95%, 100% and 64%, respectively. Median duration of response to the cladribine followed by rituximab was significantly longer than the first-line cladribine single agent in patients who received this treatment as second-line treatment (72 months vs not reached, P = 0·004). Almost all patients (94%) achieved negative minimal residual disease (MRD) after the treatment. Positive MRD during the follow up did not necessarily result in clinically relevant relapse. Cladribine followed by rituximab is highly effective even in patients with relapsed disease and HCLv, and can achieve durable remission.

  9. 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...

  10. Early Failure of Frontline Rituximab-Containing Chemo-immunotherapy in Diffuse Large B Cell Lymphoma Does Not Predict Futility of Autologous Hematopoietic Cell Transplantation

    NARCIS (Netherlands)

    Hamadani, Mehdi; Hari, Parameswaran N.; Zhang, Ying; Carreras, Jeanette; Akpek, G??rg??n; Aljurf, Mahmoud D.; Ayala, Ernesto; Bachanova, Veronika; Chen, Andy I.; Chen, Yi Bin; Costa, Luciano J.; Fenske, Timothy S.; Freytes, C??sar O.; Ganguly, Siddhartha; Hertzberg, Mark S.; Holmberg, Leona A.; Inwards, David J.; Kamble, Rammurti T.; Kanfer, Edward J.; Lazarus, Hillard M.; Marks, David I.; Nishihori, Taiga; Olsson, Richard; Reddy, Nishitha M.; Rizzieri, David A.; Savani, Bipin N.; Solh, Melhem; Vose, Julie M.; Wirk, Baldeep; Maloney, David G.; Smith, Sonali M.; Montoto, Silvia; Saber, Wael

    2014-01-01

    The poor prognosis for patients with diffuse large Bcell lymphoma (DLBCL) who relapse within 1year of initial diagnosis after first-line rituximab-based chemo-immunotherapy has created controversy about the role of autologous transplantation (HCT) in this setting. We compared autologous HCT outcomes

  11. Follicular lymphoma: in vitro effects of combining lymphokine-activated killer (LAK) cell-induced cytotoxicity and rituximab- and obinutuzumab-dependent cellular cytotoxicity (ADCC) activity.

    Science.gov (United States)

    García-Muñoz, Ricardo; López-Díaz-de-Cerio, Ascensión; Feliu, Jesus; Panizo, Angel; Giraldo, Pilar; Rodríguez-Calvillo, Mercedes; Grande, Carlos; Pena, Esther; Olave, Mayte; Panizo, Carlos; Inogés, Susana

    2016-04-01

    Follicular lymphoma (FL) is a disease of paradoxes-incurable but with a long natural history. We hypothesized that a combination of lymphokine-activated killer (LAK) cells and monoclonal antibodies might provide a robust synergistic treatment and tested this hypothesis in a phase II clinical trial (NCT01329354). In this trial, in addition to R-CHOP, we alternated the administration of only rituximab with rituximab and autologous LAK cells that were expanded ex vivo. Our objective was to determine the in vitro capability of LAK cells generated from FL patients to produce cytotoxicity against tumor cell lines and to determine rituximab- and obinutuzumab-induced cytotoxicity via antibody-dependent cellular cytotoxicity (ADCC) activity. We analyzed the LAK cell-induced cytotoxicity and rituximab (R)- and obinutuzumab (GA101)-induced ADCC activity. We show that LAK cells generated from FL patients induce cytotoxicity against tumor cell lines. R and GA101 enhance cytolysis through ADCC activity of LAK cells. Impaired LAK cell cytotoxicity and ADCC activity were detected in 50 % of patients. Percentage of NK cells in LAK infusions were correlated with the R- and GA101-induced ADCC. Our results indicate that the combination of R or GA101 and LAK cells should be an option as frontline maintenance therapy in patients with FL.

  12. 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)

    M.H.J. van Oers; M. van Glabbeke; L. Giurgea; R. Klasa; R.E. Marcus; M. Wolf; E. Kimby; M. van't Veer; A. Vranovsky; H. Holte; A. Hagenbeek

    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

  13. Combination of rituximab with autologous peripheral blood stem cell transplantation for treatment of diffuse large B-cell lymphoma:a single-center experience

    Institute of Scientific and Technical Information of China (English)

    梁赜隐

    2013-01-01

    Objective To investigate whether incorporation of rituximab into high-dose chemotherapy with autologous peripheral blood stem cell transplantation(auto-PBSCT) could improve the survival of patients with diffuse large B-cell lymphoma(DLBCL),and evaluate the safety of

  14. Dynamic contrast-enhanced, extremity-dedicated MRI identifies synovitis changes in the follow-up of rheumatoid arthritis patients treated with rituximab

    DEFF Research Database (Denmark)

    Cimmino, Marco A; Parodi, Massimiliano; Zampogna, Giuseppe

    2014-01-01

    OBJECTIVES: The aim of this study is to assess prospectively the effect of rituximab (RTX) on MRI features of wrist joint disease in patients affected by rheumatoid arthritis (RA). METHODS: Ten patients (6F/4M, mean age 52.9±15.5 years) diagnosed with IgM rheumatoid factor, anti-CCP positive, RA ...

  15. Nephrotic syndrome; is rituximab the light at the end of the tunnel in the treatment of adult steroid-dependent minimal change disease and focal segmental glomerulosclerosis?

    Science.gov (United States)

    Kronbichler, Andreas; Mayer, Gert

    2014-01-01

    Implication for health policy/practice/research/medical education: Reports on patients with steroid-dependent nephrotic syndrome and underlying minimal change disease or focal segmental glomerulosclerosis have shown promising results. There is a strong need for more trials conducted in a prospective, controlled manner to clearly recommend rituximab therapy in this indication on a regular basis.

  16. Neutralization of (NK-cell-derived) B-cell activating factor by Belimumab restores sensitivity of chronic lymphoid leukemia cells to direct and Rituximab-induced NK lysis.

    Science.gov (United States)

    Wild, J; Schmiedel, B J; Maurer, A; Raab, S; Prokop, L; Stevanović, S; Dörfel, D; Schneider, P; Salih, H R

    2015-08-01

    Natural killer (NK) cells are cytotoxic lymphocytes that substantially contribute to the therapeutic benefit of antitumor antibodies like Rituximab, a crucial component in the treatment of B-cell malignancies. In chronic lymphocytic leukemia (CLL), the ability of NK cells to lyse the malignant cells and to mediate antibody-dependent cellular cytotoxicity upon Fc receptor stimulation is compromised, but the underlying mechanisms are largely unclear. We report here that NK-cells activation-dependently produce the tumor necrosis factor family member 'B-cell activating factor' (BAFF) in soluble form with no detectable surface expression, also in response to Fc receptor triggering by therapeutic CD20-antibodies. BAFF in turn enhanced the metabolic activity of primary CLL cells and impaired direct and Rituximab-induced lysis of CLL cells without affecting NK reactivity per se. The neutralizing BAFF antibody Belimumab, which is approved for treatment of systemic lupus erythematosus, prevented the effects of BAFF on the metabolism of CLL cells and restored their susceptibility to direct and Rituximab-induced NK-cell killing in allogeneic and autologous experimental systems. Our findings unravel the involvement of BAFF in the resistance of CLL cells to NK-cell antitumor immunity and Rituximab treatment and point to a benefit of combinatory approaches employing BAFF-neutralizing drugs in B-cell malignancies.

  17. Rituximab improves the treatment results of DHAP-VIM-DHAP and ASCT in relapsed/progressive aggressive CD20+ NHL: A prospective randomized HOVON trial

    NARCIS (Netherlands)

    E. Vellenga (Edo); W.L.J. van Putten (Wim); M.B. van 't Veer (Mars); J.M. Zijlstra (Josée); W.E. Fibbe (Willem); M.H.J. van Oers (Marinus); L.F. Verdonck (Leo); P.W. Wijermans (Pierre); G. van Imhoff (Gustaaf); P.J. Lugtenburg (Pieternella); P.C. Huijgens (Peter)

    2008-01-01

    textabstractWe evaluated the role of rituximab during remission induction chemotherapy in relapsed aggressive CD20+non-Hodgkin lymphoma. Of 239 patients, 225 were evaluable for analysis. Randomized to DHAP (cisplatin-cytarabine- dexamethasone)-VIM (etoposide-ifosfamide-methotrexate)-DHAP (cisplatin-

  18. Rituximab improves the treatment results of DHAP-VIM-DHAP and ASCT in relapsed/progressive aggressive CD20(+) NHL : a prospective randomized HOVON trial

    NARCIS (Netherlands)

    Vellenga, Edo; van Putten, Wim L. J.; van't Veer, Mars B.; Zijlstra, Josee M.; Fibbe, Willem E.; van Oers, Marinus H. J.; Verdonck, Leo F.; Wijermans, Pierre W.; van Imhoff, Gustaaf W.; Lugtenburg, Pieternella J.; Huijgens, Peter C.

    2008-01-01

    We evaluated the role of rituximab during remission induction chemotherapy in relapsed aggressive CD20(+) non-Hodgkin lymphoma. Of 239 patients, 225 were evaluable for analysis. Randomized to DHAP (cisplatin-cytarabine-dexamethasone)-VIM (etoposide-ifosfamide-methotrexate)-DHAP (cisplatin-cytarabine

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

    DEFF Research Database (Denmark)

    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...

  20. An approach for conjugation of 177 Lu- DOTA-SCN- Rituximab (BioSim & its evaluation for radioimmunotherapy of relapsed & refractory B-cell non Hodgkins lymphoma patients

    Directory of Open Access Journals (Sweden)

    Parul Thakral

    2014-01-01

    Interpretation & conclusions: A favourable radiochemical purity, stability and biodistribution of the radiolabelled immunoconjugate indicate that clinical trials for evaluation of toxicity and efficacy of 177 Lu-DOTA-antiCD20 antibody-Rituximab (BioSim in patients of relapsed and refractory non Hodgkin′s lymphoma can be considered.

  1. Rituximab plus fludarabine and cyclophosphamide prolongs progression-free survival compared with fludarabine and cyclophosphamide alone in previously treated chronic lymphocytic leukemia

    DEFF Research Database (Denmark)

    Robak, Tadeusz; Dmoszynska, Anna; Solal-Céligny, Philippe;

    2010-01-01

    Rituximab, a monoclonal antibody that targets the CD20 cell surface antigen, has clinical activity in patients with non-Hodgkin's lymphoma and other B-lymphocyte disorders when administered alone or in combination with chemotherapy. Promising results have previously been reported in nonrandomized...

  2. Combination therapy with rituximab and cyclophosphamide in the treatment of anti-neutrophil cytoplasmic antibodies (ANCA positive pulmonary hemorrhage: case report

    Directory of Open Access Journals (Sweden)

    Lehman Thomas JA

    2011-10-01

    Full Text Available Abstract Anti-neutrophil cytoplasmic antibody (ANCA-associated vasculitis (AAV with pulmonary hemorrhage is rare in childhood. Standard treatment includes corticosteroids and cyclophosphamide (CYC, which is associated with a high level of toxicity. We report a white female with ANCA positive pulmonary hemorrhage who was treated with cyclophosphamide (CYC and rituximab (RTX combination therapy.

  3. Budget impact analysis of the use of rituximab in the treatment of rheumatoid arthritis in Italy

    Directory of Open Access Journals (Sweden)

    Maurizio Benucci

    2009-01-01

    Full Text Available Objective: a Budget Impact analysis was performed to evaluate cost implications for the Italian National Health Service (NHS of the introduction of rituximab (RTX in the treatment of rheumatoid arthritis (RA. Methods: RA patients eligible to treatment with a second-line biologic DMARD (Disease Modifying Antirheumatic Drugs were identified and quantified and available strategies for their management were explored. Costs associated with the different alternatives were estimated, and the impact on the NHS budget was estimated using a cohort simulation based on a Markov chain with a time horizon of 5 years and 1-year cycles. Seven alternative strategies were analyzed, each of them starting after the failure of a first anti-TNFα: 1 the use of a second and a third anti-TNFα; 2 the use of a second anti-TNFα followed by RTX; 3 the use of a second anti-TNFα followed by abatacept (ABAT; 4 the use of RTX as a second biological line, followed by an anti-TNFα; 5 the use of ABAT as a second biological line, followed by an anti-TNFα; 6 the use of RTX as a second biological line, followed by ABAT; 7 the use of ABAT as a second biological line, followed by RTX. Only direct medical costs were considered: drug acquisition, administration, incidental premedication and monitoring exams. Results: Italian patients eligible to second biological line therapies (RA patients refractory or intolerant to at least one anti-TNFα therapy were estimated in about 650 per year. The adoption of RTX as a second line therapy produced a substantial saving in total costs (-33% at the fifth year with respect to the strategy with RTX as third line and the one with only anti-TNFα (the last two resulting substantially cost-equivalent. The number of patients in active treatment (biologic DMARD per unit cost resulted of about 8.1 patient-years/100,000 € with the strategy based only on anti-TNFα and increased of 10% with RTX as a third line. The strategy of RTX as a second line

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

    Energy Technology Data Exchange (ETDEWEB)

    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

  5. 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

    2015-02-27

    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.

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

    Directory of Open Access Journals (Sweden)

    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

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

    Directory of Open Access Journals (Sweden)

    Flavia C. F. Pimenta

    2008-10-01

    Full Text Available A macroglobulinemia de Waldenström (MW é uma patologia rara dos linfócitos B caracterizada pela produção monoclonal de IgM, e que pode manifestar-se clinicamente com fadiga, astenia, perda de peso, sangramento de mucosas e do trato gastrintestinal, lifonodonomegalias, hepatoesplenomegalia e alterações neurológicas. A doença é mais comum em pacientes idosos, e seus sintomas são decorrentes da hiperviscosidade sangüínea. Na MW observa-se hipergamaglobulinemia com pico monoclonal na eletroforese de proteínas séricas, níveis elevados de IgM e demais imunoglobulinas normais ou diminuídas, imunofenotipagem com linfócitos B CD19+, CD20+ e CD24+, aspirado de medula óssea hipercelular, e biópsia de medula óssea hipercelular com infiltração difusa de linfócitos, linfócitos plasmocitóides e plasmócitos. Atualmente, anticorpos monoclonais estão sendo usados na terapêutica da MW com grande sucesso. O rituximabe, anticorpo monoclonal anti -CD20, tem mostrado excelentes resultados no tratamento da MW, inclusive naqueles indivíduos que não obtiveram resposta adequada ao tratamento convencional. Nós reportamos o caso de uma mulher de 78 anos de idade com história de fadiga, astenia, anorexia, sonolência, inquietação, urticária, dificuldade para deambular e perda excessiva de peso, aproximadamente 22 kg em um período de cinco meses, cujo tratamento foi realizado com rituximabe. O objetivo deste relato é apresentar uma paciente com diagnóstico de MW e revisar aspectos clínicos e terapêutico atual da doença.Waldenström's macroglobulinemia is a rare pathology of B lymphocytes characterized by the production of monoclonal IgM, causing clinical manifestations which may include fatigue, asthenia, weight loss, bleeding of the mucosa and intestinal tract, lymphadenomegaly, hepatosplenomegaly and neurological alterations. The disease is more frequent among elderly patients and its symptoms are a result of the hyperviscosity of

  8. Hyperinfection by Strongyloides stercoralis probably associated with Rituximab in a patient with mantle cell lymphoma and hyper eosinophilia Hiperinfección por Strongyloides stercoralis probablemente asociada con Rituximab en una paciente con linfoma e hipereosinofilia

    Directory of Open Access Journals (Sweden)

    Renzo Nino Incani

    2010-08-01

    Full Text Available The first report to our knowledge, of hyperinfection by Strongyloides stercoralis (HS and hypereosinophilia, associated to immune suppression by Rituximab (the only drug received for the last one year and 10 months, in a patient with mantle-cell lymphoma (MCL, is presented. The patient has a 3-year history of MCL, and developed two accesses of HS during 2008, including meningitis, pneumonia and presence of larvae of S. stercoralis in the lungs. We had a unique chance to look at cytotoxicity of filariform larvae in the expectoration after Ivermectin treatment, showing immobilization and death of larvae, associated with eosinophils attached to the cuticle of the parasite.Se presenta el primer reporte, hasta donde tengamos información, de hiperinfección por Strongyloides stercoralis (HS e hipereosinofilia asociados a inmunosupresión por Rituximab (el único medicamento recibido durante 1 año y 10 meses, en un paciente con linfoma de células del manto (LCM. La paciente tuvo una historia de 3 años con LCM, y desarrolló 2 accesos de HS durante el 2008, incluyendo meningitis, neumonía y presencia de larvas de S. stercoralis en los pulmones. Se tuvo la oportunidad única de observar la citotoxicidad contra las larvas filariformes en la expectoración, luego del tratamiento con Ivermectina, mostrando la inmovilización y muerte de las larvas, asociada a la presencia de eosinófilos adheridos a la cutícula del parásito.

  9. Effective Treatment of Rheumatoid Arthritis-Associated Interstitial Lung Disease by B-Cell Targeted Therapy with Rituximab

    Directory of Open Access Journals (Sweden)

    Wolfgang Hartung

    2012-01-01

    Full Text Available Rheumatoid arthritis- (RA- associated interstitial lung disease (RA-ILD is the extra-articular complication with most adverse impact on the quality of life and survival in RA patients. However, treatment options are limited and controlled studies are lacking. Here, we present the case of a 66-year-old patient suffering from severe RA-ILD, which has been successfully treated with Rituximab (RTX. After failure of conventional DMARD therapy, our patient showed sustained improvement of clinical pulmonary parameters as well as joint inflammation following B-cell depletion with RTX. The six-minute-walk test improved from 380 meters to 536 meters and the forced vital capacity from 2.49 liters to 3.49. The disease activity score could be reduced from 7.7 to 2.8. Therefore, RTX might be considered as an alternative treatment for RA-ILD in patients not responding to conventional DMARD therapy.

  10. Lymphomatoid Granulomatosis of Central Nervous System and Lung Driven by Epstein Barr Virus Proliferation: Successful Treatment with Rituximab

    Directory of Open Access Journals (Sweden)

    Ruben Fernandez

    2014-02-01

    Full Text Available 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 of the bronchoalveolar lavage was positive for EBV and biopsy of lung node yielded a diagnosis of LYG, grade III. Shortly after initiation of treatment with chemotherapy, neurologic deterioration appeared. Radiologic 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 radiological and clinical improvement. After completion of treatment with immunochemotherapy, an autologous stem cell transplantation was performed. Patient stays in remission one year after diagnosis.

  11. 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 < 36 months after frontline chemo-immunotherapy. Toxicity was mainly of mild to moderate severity (grade 1–2). 10 (25%) patients had diarrhea (grade 1 in 9 [22.5%] patients, grade 2 in 1 [2.5%]), bleeding events occurred in 14 (35%) patients (8 [20%] patients with grade 1, 5 [12.5%] patients grade 2, and 1 [2.5%] grade 3), nausea in 15 (37.5) patients (10 [25%] grade 1, 5 [12.5%] grade 2), and fatigue in 7 (17.5%) patients (4 [10%] grade 1, 3 [7.5%] grade 2). Grade 3 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

  12. Fludarabine, cyclophosphamide, and rituximab (FCR) plus GM-CSF as frontline treatment for patients with Chronic Lymphocytic Leukemia

    Science.gov (United States)

    Strati, Paolo; Ferrajoli, Alessandra; Lerner, Susan; O’Brien, Susan; Wierda, William; Keating, Michael J; Faderl, Stefan

    2015-01-01

    FCR, the standard of care for frontline treatment of CLL patients, is associated with a high rate of neutropenia and infectious complications. GM-CSF reduces myelosuppression and can potentiate rituximab activity. We conducted a clinical trial combining GM-CSF with FCR for frontline treatment of 60 CLL patients. Eighty-six percent completed all 6 courses and 18% discontinued GM-CSF for toxicity; grade 3–4 neutropenia was observed in 30% of cycles, and severe infections in 16% of cases. ORR was 100%. Both median EFS and OS have not been reached. Longer EFS was associated with favorable cytogenetic. GM-CSF led to a lower frequency of infectious complications than the historical FCR group, albeit similar EFS and OS. PMID:23808813

  13. Rituximab treatment in a case of antisynthetase syndrome with severe interstitial lung disease and acute respiratory failure

    Directory of Open Access Journals (Sweden)

    Zappa Maria

    2011-08-01

    Full Text Available Abstract We present a case of severe interstitial pneumonitis, mild polyarthritis and polymyositis, and Raynaud's syndrome with the presence of anti-Jo-1 antibodies, which had been diagnosed as anti-synthetase syndrome. The presence, however, of anti-Ro/SSA antibodies led us to understand that we were dealing here with a more severe form of interstitial lung disease. The patient was treated for acute respiratory failure but he showed resistance to glucocorticoids and cyclosporine. Thus, he was treated with infusions of anti-CD20 therapy (rituximab: his clinical conditions improved very rapidly and a significant decrease in the activity of pulmonary disease was detected using high-resolution computerized tomography (HRCT of the thorax and pulmonary function tests.

  14. Successful experience of rituximab therapy for systemic sclerosis-associated interstitial lung disease with concomitant systemic lupus erythematosus.

    Science.gov (United States)

    Sumida, Hayakazu; Asano, Yoshihide; Tamaki, Zenshiro; Aozasa, Naohiko; Taniguchi, Takashi; Takahashi, Takehiro; Toyama, Tetsuo; Ichimura, Yohei; Noda, Shinji; Akamata, Kaname; Miyazaki, Miki; Kuwano, Yoshihiro; Yanaba, Koichi; Sato, Shinichi

    2014-05-01

    Previous studies have demonstrated that B cells play critical roles in autoimmune disorders including systemic sclerosis (SSc) and systemic lupus erythematosus (SLE). However, the effectiveness of rituximab (RTX), a chimeric anti-CD20 antibody, for SSc-associated interstitial lung disease (ILD) or SLE disease activity remains controversial. We herein report an SSc patient with severely progressed ILD and concomitant SLE treated by two cycles of RTX at baseline and half a year later. This treatment improved ILD and SLE activities, along with reduction of dermal sclerosis and serum anti-topoisomerase I antibody levels. In addition, our detailed time-course data indicate that half a year may be appropriate as an interval between each cycle of RTX therapy aimed at SSc-associated ILD or SLE. Overall, the current report could pave the way to establish RTX as a disease-modifying drug for patients with SSc and/or SLE showing resistance to other already approved medications.

  15. Rituximab in Combination with CHOP, an Effective and Well-tolerated Salvage Regimen for Diffuse Large B-Cell Lymphoma

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    OBJECTIVE To evaluate the clinical effect of the R-CHOP regimen (rituximab in combination with cyclophosphamide, epirubicin, vincristine and prednisone) in treating refractory or relapsed diffuse large B-cell lymphoma (DLBCL), as a salvage therapy for DLBCL.METHODS Eighteen patients with refractory or relapsed DLBCL who were treated with the R-CHOP regimen from 2001 to 2006 in hospitals in Jilin Province were analyzed retrospectively. The response rate, change of serum lactate dehydrogenase (LDH), time to progression (TTP) and toxicity were observed.RESULTS The R-CHOP regimen can achieve a higher response rate, decrease serum LDH to a larger extent and obtain longer TTP than a conventional secondary regimen. The main adverse effects were similar to conventional chemotherapy.CONCLUSION The R-CHOP regimen is one of the most effective secondary therapies for DLBCL.

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

    Energy Technology Data Exchange (ETDEWEB)

    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

  17. Targeted biological therapies for Graves' disease and thyroid-associated ophthalmopathy. Focus on B-cell depletion with Rituximab

    DEFF Research Database (Denmark)

    Hegedüs, Laszlo; Douglas, Raymond S; Nielsen, Claus H

    2011-01-01

    Based on experience from the treatment of other autoimmune diseases and because of the limitations imposed by existing therapeutic options for Graves' disease (GD) and thyroid-associated ophthalmopathy (TAO), rituximab (RTX) was recently proposed as a novel therapy option. Here, we summarize...... the rationale for using RTX; give an overview of the possible mechanisms of action; and give an account of its effects and side-effects when used in GD and TAO. Scant evidence, originating from only a few methodologically inhomogeneous studies, suggests that RTX may prolong remission for hyperthyroidism over...... favourably to conventional therapy. It is the first in what is likely to be a series of new and emerging treatments specifically targeting relevant components of the immune system. Further studies will hopefully lead to improved and better tailored, individualized therapy for GD and especially TAO....

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

    Directory of Open Access Journals (Sweden)

    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.

  19. Combination of bendamustine and rituximab in the management of relapsed and refractory chronic lymphocytic leukemia: the results of retrospective study

    Directory of Open Access Journals (Sweden)

    S. V. Semochkin

    2015-01-01

    Full Text Available Efficacy and safety results of rituximab and bendamustine combination (Scheme BR in patients with relapsed and refractory chronic lymphocytic leukemia (CLL are presented. From 01.2012 to 04.2013, the treatment was initiated in 43 patients (21 with relapses are sensitive to the last line of therapy; 22 – with refractory CLL. Median age at start of therapy was 63.5 years (range from 43 to 81 years. In 40 patients response was evaluated according to NCI-WG criteria (1996. Complete remission (CR is documented in 5 (12.5 % cases, partial (PR or nodular partial remission (nPR in 17 (42.5 % cases. MRD-negative CR was achieved in 1 (20.0 % of 5 patients with CR. With 23.5 months of median follow-up for surviving patients 2-year progression-free survival (PFS was 47.2 ± 8.5 % (median – 18.5 months, overall survival (OS – 66.9 ± 7.9 % (median not achieved. Hematological toxicity Grade 3–4 occurred in 15 (34.9 % cases, same degree infectious complicationsin 5 (11.6 % cases. Patients received 3 or more therapy lines before this treatment (37.5 ± 16.1 % against 74.7 ± 8.3 %; p = 0.016, with «bulky disease» more than 10 cm (0.0 % vs. 75.4 ± 7.5 %; p < 0.001 and received rituximab in combination with chemotherapy in the previous lines, compared to the «naive» cases (44.1 ± 10.5 % against 92.9 ± 6.9 %; p = 0.009 have significantly worsened 2-year OS.

  20. Discrepancy of B cell frequency between periphery and spleen after rituximab treatment in ABO-incompatible liver transplantation.

    Science.gov (United States)

    Iso, Yukihiro; Sawada, Tokihiko; Kita, Junji; Shiraki, Takayuki; Sakuraoka, Yuki; Kato, Masato; Shimoda, Mitsugi; Kubota, Keiichi

    2013-10-01

    ABO-incompatible living-donor liver transplantation (ABO-LDLT) is generally more difficult to perform than ABO-incompatible kidney transplantation. Despite introduction of rituximab, ABO-LDLT in non-responders is a still difficult issue. A 23-year-old woman with primary sclerosing cholangitis underwent LDLT. The recipient's blood type was 0(+) and the donor's was B(+). Rituximab was infused twice on preoperative day (POD) 14 and 7. Plasma exchange (PE) was performed on PODs 5, 3, 2, and 1. However, repeated PE failed to decrease the anti-B antibody titer. On the other hand, preoperative esophagogastroscopy revealed esophageal varices with red color sign. Therefore, simultaneous liver transplantation and Hassab operation were performed. The donor left lobe of the liver was orthotopically transplanted into the recipient following Hassab operation. Flow cytometry on the day of surgery showed that the frequencies of B cells (CD20+) and memory B cells (CD20+/CD27+) in the peripheral blood were 0.9% and 0.3%, respectively; flow cytometry of cells recovered from the spleen revealed that the frequencies of B cells and memory B cells were 2.5% and 2.4%, respectively. Acute cellular rejection occurred on POD 15, and was treated by steroid pulse therapy, leading to a decrease in the anti-B antibody titer. The liver was functioning well on POD 390 (AST 19, ALT 34). In non-responders to ABO-LDLT, anti-donor blood type antibody-producing cells remains in the spleen after the conventional preoperative regimen. Splenectomy is an option for ABO-LDLT non-responders.

  1. Severe multiorganic flare of systemic lupus erythematosus successfully treated with rituximab and cyclophosphamide avoiding high doses of prednisone.

    Science.gov (United States)

    Gonzalez-Echavarri, C; Pernas, B; Ugarte, A; Ruiz-Irastorza, G

    2014-03-01

    Both acute pancreatitis and diffuse alveolar haemorrhage are rare conditions associated with systemic lupus erythematosus (SLE). In this case report, a 23-year-old female with SLE was diagnosed with lupus-associated pancreatitis and, within a few days and despite initial therapy with pulse methyl-prednisolone, subsequently suffered an acute respiratory failure due to a diffuse alveolar haemorrhage. The patient was admitted to the intensive care unit and treatment was intensified with cyclophosphamide and rituximab, which shortly induced the complete remission of SLE with resolution of both clinical conditions. She completed treatment with six pulses of cyclophosphamide followed by azathioprine, hydroxychloroquine and prednisone at initial doses of 20 mg/d with rapid tapering to 5 mg/d, without relapse of the disease during the following year. This case can illustrate that, even in severe, life-threatening SLE flares, it is possible to avoid high-dose prednisone, which has been associated with severe side effects, including infections. Acute pancreatitis and diffuse alveolar haemorrhage are rare conditions caused by SLE. DAH can be a life-threatening complication, with an early mortality of at least 50%. When facing such severe SLE activity, there is a general tendency to use high doses of prednisone as the initial therapy, maintaining such high doses for long periods of time, even after the clinical situation has subsided. We report a case of a young woman with SLE, suffering from acute pancreatitis and diffuse alveolar haemorrhage, who was successfully treated with pulse methyl-prednisolone, hydroxychloroquine, cyclophosphamide and rituximab, combined with medium doses of prednisone.

  2. First-line treatment with brief-duration chemotherapy plus rituximab in elderly patients with intermediate-grade non-Hodgkin's lymphoma: phase II trial.

    Science.gov (United States)

    Hainsworth, John D; Litchy, Sharlene; Lamb, M Ray; Rodriguez, Gladys I; Scroggin, Carroll; Greco, F Anthony

    2003-06-01

    This study was designed to evaluate the feasibility, toxicity, and efficacy of rituximab added to the VNCOP-B (etoposide/mitoxantrone/cyclophosphamide/vincristine/prednisone/bleomycin) combination regimen for the treatment of elderly patients with large B-cell lymphoma. Previously untreated patients > or = 65 years of age with stage II, III, or IV large B-cell non-Hodgkin's lymphoma were treated with a modified VNCOP-B regimen with weekly chemotherapy for 8 weeks. In addition, patients received rituximab 375 mg/m2 intravenously on weeks 1, 2, 3, 4, 6, and 8. All patients received prophylactic granulocyte colony-stimulating factor (G-CSF) or granulocyte-macrophage colony-stimulating factor (GM-CSF) during the 8 weeks of treatment. Between August 1999 and February 2002, 41 patients entered this multicenter phase II trial. The median age was 74 years, and 54% of patients had high-risk tumors (age-adjusted International Prognostic Index scores of 2 or 3). Sixty-eight percent of patients completed the 8 weeks of therapy. Overall response rate was 66%; actuarial progression-free survival rate at 2 years was 59%, with a 57% actuarial overall 2-year survival rate. Patients > or = 75 years of age had similar treatment outcomes compared with younger patients. Toxicity with this regimen was predominantly related to chemotherapy; rituximab was well tolerated. Grade 3/4 neutropenia occurred in 83% of patients even with routine use of prophylactic G-CSF or GM-CSF. Treatment-related death occurred in 4 patients (10%). VNCOP-B plus rituximab is efficacious, producing 2-year progression-free survival rates that compare favorably with those of other active regimens in this patient group. Hematologic toxicity was increased compared with previous reports with VNCOP-B alone, as evidenced by the treatment-related mortality rate of 10% in the present study. Differences in toxicity may have been caused by the addition of rituximab, the modified etoposide schedule, or the differences in

  3. Obinutuzumab (GA101) compared to rituximab significantly enhances cell death and antibody-dependent cytotoxicity and improves overall survival against CD20(+) rituximab-sensitive/-resistant Burkitt lymphoma (BL) and precursor B-acute lymphoblastic leukaemia (pre-B-ALL): potential targeted therapy in patients with poor risk CD20(+) BL and pre-B-ALL.

    Science.gov (United States)

    Awasthi, Aradhana; Ayello, Janet; Van de Ven, Carmella; Elmacken, Mona; Sabulski, Anthony; Barth, Matthew J; Czuczman, Myron S; Islam, Humayun; Klein, Christian; Cairo, Mitchell S

    2015-12-01

    Obinutuzumab is a novel glycoengineered Type-II CD20 monoclonal antibody. CD20 is expressed in approximately 100% of children and adolescents with Burkitt lymphoma (BL) and 40% with precursor B-cell acute lymphoblastic leukaemia (pre-B-ALL). We evaluated the anti-tumour activity of obinutuzumab versus rituximab against rituximab-resistant (Raji 4RH) and -sensitive (Raji) BL and pre-B-ALL (U698-M) cells in vitro and in human BL or Pre-B-ALL xenografted mice. We demonstrated that obinutuzumab compared to rituximab significantly enhanced cell death against Raji 35·6 ± 3·1% vs. 25·1 ± 2·0%, (P = 0·001), Raji4RH 19·7 ± 2·2% vs. 7·9 ± 1·5% (P = 0·001) and U-698-M 47·3 ± 4·9% vs. 23·2 ± 0·5% (P = 0·001), respectively. Obinutuzumab versus rituximab also induced a significant increase in antibody-dependent cellular cytotoxicity (ADCC) with K562-IL15-41BBL expanded NK cells against Raji 73·8 ± 8·1% vs. 56·81 ± 4·6% (P = 0·001), Raji-4RH 40·0 ± 1·6% vs. 0·5 ± 1·1% (P = 0·001) and U-698-M 70·0 ± 1·6% vs. 45·5 ± 0·1% (P = 0·001), respectively. Overall survival in tumour xenografted mice receiving 30 mg/kg of obinutuzumab was significantly increased when compared to those receiving 30 mg/kg of rituximab in BL; Raji (P = 0·05), Raji4RH (P = 0·02) and U698-M (P = 0·03), respectively. These preclinical data suggest obinutuzumab is significantly superior to rituximab in inducing cell death, ADCC and against rituximab-sensitive/-resistant BL and pre-B-ALL xenografted mice. Taken together, these preclinical results provide evidence to suggest that future investigation of obinutuzumab is warranted in patients with relapsed/refractory CD20(+) BL and/or pre-B-ALL.

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

    Directory of Open Access Journals (Sweden)

    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.

  5. Survival impact of rituximab combined with ACVBP and upfront consolidation autotransplantation in high-risk diffuse large B-cell lymphoma for GELA

    Science.gov (United States)

    Fitoussi, Olivier; Belhadj, Karim; Mounier, Nicolas; Parrens, Marie; Tilly, Hervé; Salles, Gilles; Feugier, Pierre; Ferme, Christophe; Ysebaert, Loic; Gabarre, Jean; Herbrecht, Raoul; Janvier, Maud; Van Den Neste, Eric; Morschhauser, Franck; Casasnovas, Olivier; Ghesquieres, Hervé; Anglaret, Bruno; Brechignac, Sabine; Haioun, Corinne; Gisselbrecht, Christian

    2011-01-01

    Background As rituximab combined with CHOP improves complete remission and overall survival in diffuse large B-cell lymphoma, intensified chemotherapy followed by autologous stem-cell transplantation has also been advocated for high-risk patients. The aim of this study was to establish whether or not combining rituximab with high-dose chemotherapy and auto-transplantation also benefits patient survival. Design and Methods The LNH2003-3 study was a phase II trial including diffuse large B-cell lymphoma patients with 2 or 3 International Prognostic Index factors. They received four cycles of intensive biweekly chemotherapy with rituximab, doxorubicine, cyclophosphamide, vindesine, bleomycine, prednisolone (R-ACVBP) followed by auto-transplantation in responding patients. Two hundred and nine patients under 60 years of age were included in the study and 155 responding patients underwent auto-transplantation. In addition, a case-control study was performed by matching (1:1) 181 patients treated with R-ACVBP with ACVBP patients not given rituximab but submitted to auto-transplantation from the previous LNH1998-3 trial. Results With a median follow up of 45 months, 4-year progression-free survival and overall survival were estimated at 76% (CI: 69–81) and 78% (CI: 72–83), respectively. There was no difference between patients with 2 or 3 International Prognostic Index factors. Four year progression-free survival was significantly higher in R-ACVBP than ACVBP patients (74% vs. 58%; P=0.0005). There was also a significant increase in 4-year overall survival (76% vs. 68%; P=0.0494). Conclusions In high-risk diffuse large B-cell lymphoma patients, treatment with R-ACVBP followed by auto-transplantation results in a 78% 4-year overall survival which should be compared to other approaches. (Clinicaltrials.gov identifier: NCT00144807) PMID:21546499

  6. RITUXIMAB TREATMENT EFFICACY IN PATIENTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS REFRACTORY TO STANDARD THERAPY IN THE LONG-TERM FOLLOW-UP

    OpenAIRE

    M. E. Tsanyan; S K Soloviev; A. V. Torgashina; E N Aleksandrova; S G Radenska-Lopovok; E. V. Nikolaeva; E L Nasonov

    2014-01-01

    Objective. To evaluate the efficacy and safety of rituximab (RTM) treatment in the long-term follow-up of patients with systemic lupus erythematosus (SLE) refractory to standard therapy. Material and methods. RTM therapy was prescribed to 97 SLE patients with high disease activity and insufficient effica- cy of using high doses of glucocorticoids (GC) and cytostatics. The median follow-up time (25th; 75th percentiles) was 18 [12; 36] months. The most common clinical manifestations of SLE incl...

  7. 利妥昔单抗在儿童血液病中的应用%Rituximab in the treatment of children's hematological disease

    Institute of Scientific and Technical Information of China (English)

    朱嘉莳; 蒋慧

    2013-01-01

    抗CD20人鼠嵌合型单克隆抗体利妥昔单抗可通过多种机制杀伤B细胞,目前广泛应用于治疗CD20阳性淋巴瘤以及某些免疫相关性疾病,如免疫性血小板减少性紫癜、自身免疫性溶血性贫血、Evans综合征、移植后淋巴增殖性疾病和系统性红斑狼疮等.本文综述利妥昔单抗在儿童血液病中的临床应用.%Rituximab is a chimeric mouse-human monoclonal antibody against the CD 20 antigen, which can kill the B cell. Rituximab is widely used in patients with CD20 positive lymphoma and some other immune related diseases, such as immune thrombocytopenic purpura, autoimmune hemolytic anemia, Evans syndrome, post transplant lymphoproliferative disease and systemic lupus erythematosus. This review summarizes the research progress of rituximab in the treatment of children with hematological disease.

  8. Orthotopic liver transplantation after successful treatment with anti-CD20 monoclonal antibody (rituximab) for severe steroid-resistant autoimmune hemolytic anemia: a case report.

    Science.gov (United States)

    Annicchiarico, B E; Siciliano, M; Avolio, A W; Agnes, S; Bombardieri, G

    2009-05-01

    Chronic hepatitis C virus (HCV) infection has been associated with a wide number of immunologic disorders, ranging from clinically silent laboratory abnormalities (eg, autoantibody positivity) to severe systemic diseases (eg, cryoglobulinemic vasculitis). Autoimmune hemolytic anemia (AIHA), due to the production of antibodies against erythrocyte membrane antigens, is an uncommon extrahepatic manifestation in the setting of chronic hepatitis C. Herein we have reported the case of a 57-year-old woman with decompensated HCV-related cirrhosis awaiting orthotopic liver transplantation (OLT) who experienced severe AIHA. After 1 month of treatment with prednisone (1 mg/kg body weight/d), there was no significant amelioration of anemia. Rituximab, an anti-CD20 monoclonal antibody that depletes B-lymphocytes reducing serum immunoglobulins, was initiated (375 mg/m(2) IV, weekly for 4 weeks) with a prompt, sustained increase in hemoglobin. The drug was well tolerated; it did not interfere with the course of the liver disease. Thirty-one months after rituximab therapy with resolution of AIHA, the patient successfully underwent OLT using immunosuppression with tacrolimus and low-dose steroids. The patient was discharged on postoperative day 36. No infectious event occurred in the postoperative period. At 18 months follow-up after OLT, there has been no infectious or hematological event. Our experience supported the safety of rituximab use in patients with advanced HCV-related liver disease before OLT.

  9. 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.

  10. Progressive multifocal leukoencephalopathy secondary to rituximab-induced immunosuppression and the presence of John Cunningham virus: a case report and literature review

    Directory of Open Access Journals (Sweden)

    Deirdre Kelly, MBBCH

    2016-09-01

    Full Text Available We present the case of a 60-year-old man who developed subacute neurologic changes, in the setting of stage III non-Hodgkin's follicular lymphoma, and was treated with induction chemotherapy, followed by a year of maintenance rituximab. Magnetic resonance imaging of the brain with gadolinium was pathognomonic for progressive multifocal leukoencephalopathy (PML. He was treated with sequential plasmapheresis and intravenous immunoglobulin with clinical improvement. A literature review of the diagnostic workup of rituximab-induced PML was undertaken. This case and the literature review demonstrate the important role of magnetic resonance imaging of the brain in diagnosis and follow-up of rituximab-induced PML. Specific radiologic features in combination with cerebrospinal fluid can be diagnostic and avoid the morbidity and mortality of a diagnostic brain biopsy. Plasmapheresis and intravenous immunoglobulin have a therapeutic role and demonstrate symptom improvement and disease control. Follow-up imaging in combination with clinical response is important in demonstrating a treatment response.

  11. Acquired haemophilia A in a patient with chronic hepatitis C virus infection receiving treatment with pegylated interferon plus ribarivin: role of rituximab.

    Science.gov (United States)

    Fernández de Palencia Espinosa, M Á; Arocas Casañ, V; Garrido Corro, B; de la Rubia Nieto, A

    2013-01-01

    Antecedentes: la hemofilia adquirida es un trastorno infrecuente causado por el desarrollo de inhibidores del factor de coagulación. Para eliminarlos, se requiere tratamiento con corticoides y fármacos citotóxicos. Métodos: describimos el caso del uso de rituximab en hemofilia adquirida refractaria al tratamiento convencional en un hombre de 63 años con infección crónica por el virus de la hepatitis C y que estaba recibiendo tratamiento con interferón pegilado a-2a y ribarivina. Resultados: tras 21 semanas de tratamiento antivírico, el paciente fue ingresado en el hospital por un gran hematoma en la musculatura abdominal. La concentración de factor VIII era nula y el título de inhibidor fue de 345 unidades Bethesda. Se administró tratamiento inmunosupresor oral con metilprednisolona y ciclofosfamida durante 1 mes, con escasa mejoría. Así pues, se sustituyó la ciclofosfamida por una dosis semanal de rituximab intravenoso. Dos meses después, la concentración de factor VIII se normalizó y el título de inhibidor era indetectable. Conclusión: Rituximab puede ser útil en el tratamiento de la hemofilia adquirida resistente al tratamiento estándar.

  12. A monocentric retrospective study comparing pulse cyclophosphamide therapy versus low dose rituximab in the treatment of refractory autoimmune hemolytic anemia in adults.

    Science.gov (United States)

    Fu, Rong; Yan, Siyang; Wang, Xiaoming; Wang, Guojin; Qu, Wen; Wang, Huaquan; Wu, Yuhong; Liu, Hong; Song, Jia; Guan, Jin; Xing, Limin; Ruan, Erbao; Li, Lijuan; Liu, Hui; Shao, Zonghong

    2016-10-01

    This retrospective study aims at confirming the efficacy and safety of low dose rituximab and pulse cyclophosphamide in the treatment of refractory AIHA in adults and making comparison of the two. Forty-nine adult patients with refractory AIHA have been enrolled. Results showed low dose rituximab combined with steroid therapy (group B) got more CR (78.9 %, 15/19) compared to that in intermittent intravenous cyclophosphamide combined with steroid therapy (group A) (42.1 %, 8/19) (P = 0.04) at 6 months after treatment. The hemoglobin level in group B was higher than group A at the time point of 1 month (P = 0.02) after treatments. The RFS in group A was 87.9 % at 6 months and 82.7 % at 12 months, which were no significant difference with group B (91.1 % at 6 months and 86.0 % at 12 months) (P = 0.81). Both the two therapies were well tolerated with pulmonary infections as the most common side effects. In conclusion, low dose rituximab combined with steroid therapy presents to be a better choice in the treatment of refractory AIHA in adults comparing with pulse cyclophosphamide therapy.

  13. Thyroid dose of I-131 absorbed by the internal organs of a pregnant woman; Dosis tiroidea de I-131 absorbida por los organos internos de una embarazada

    Energy Technology Data Exchange (ETDEWEB)

    Arcos P, A.; Manzanares A, E.; Vega C, H.R.; Leon, C.L. de [Cuerpo Academico de Radiobiologia de la Universidad Autonoma de Zacatecas (Mexico)]. e-mail: emanz_44@yahoo.com

    2007-07-01

    The use of nuclear techniques, for diagnosis or treatment, generates stress in the patient and its relatives. During the pregnancy some sufferings related with the thyroid gland can be presented. If the patient is pregnant, OEP or NOEP, the stress comes from the fear to that the product can it turns affected. The dose is calculated that the Iodine 131, captured by the thyroid of a woman with three months of pregnancy, it deposits in the brain, stomach, heart, kidneys, liver, lungs, ovaries, pancreas, thymus, spleen and in the uterus. The thymus is the organ that receives the biggest dose. (Author)

  14. Thyroid Remnant Estimation by Diagnostic Dose I131 Scintigraphy or TcO4-99m Scintigraphy after Thyroidectomy: A Comparison with Therapeutic Dose I131 Imaging

    Directory of Open Access Journals (Sweden)

    Guanghui Liu

    2016-01-01

    Full Text Available In this clinical study, we have compared routine diagnostic dose 131I scan and TcO4-99m thyroid scintigraphy with therapeutic dose 131I imaging for accurate thyroid remnant estimation after total thyroidectomy. We conducted a retrospective review of the patients undergoing total thyroidectomy for differentiated thyroid carcinoma (DTC and subsequently receiving radioactive iodine (RAI treatment to ablate remnant thyroid tissue. All patients had therapeutic dose RAI whole body scan, which was compared with that of diagnostic dose RAI, TcO4-99m thyroid scan, and ultrasound examination. We concluded that therapeutic dose RAI scan reveals some extent thyroid remnant in all DTC patients following total thyroidectomy. Diagnostic RAI scan is much superior to ultrasound and TcO4-99m thyroid scan for the postoperative estimation of thyroid remnant. Ultrasound and TcO4-99m thyroid scan provide little information for thyroid remnant estimation and, therefore, would not replace diagnostic RAI scan.

  15. Rituximab use in young adults diagnosed with juvenile idiopathic arthritis unresponsive to conventional treatment: report of 6 cases.

    Science.gov (United States)

    Sakamoto, Ana Paula; Pinheiro, Marcelo M; Barbosa, Cássia Maria Passarelli Lupoli; Fraga, Melissa Mariti; Len, Claudio Arnaldo; Terreri, Maria Teresa

    2015-01-01

    Juvenile idiopathic arthritis (JIA) is the most common rheumatic disease in childhood. Without an effective therapy, patients may progress quickly to functional disability. Recently, depletion of B cells emerged as a new approach for the treatment of autoimmune diseases, including JIA. We describe six cases of JIA patients followed at a referral center for Rheumatology and Pediatric Rheumatology, submitted to treatment with rituximab (RTX) after refractoriness to three anti-TNF agents. Patients received RTX cycles with two infusions every six months. Response to treatment was assessed by DAS28, HAQ/CHAQ, and an overall assessment by the doctor and the patient. Of our six patients, four were girls (mean age at onset of disease: 6.1 years; mean disease evolution time: 15.1 years; mean age upon receiving RTX: 21.6 years). Four patients belonged to polyarticular subtype (1 rheumatoid factor [RF]-negative, 3 FR-positive), a patient with systemic JIA subtype with a polyarticular course and arthritis related to enthesitis. Of our six patients, five responded to treatment; and during the course of 12 months, the clinical response was maintained, although not sustained. However, discontinuation by infusion reactions caused the withdrawal of RTX in two patients. The use of RTX in JIA is restricted to cases refractory to other biological agents and, even considering that this study was held in a small number of advanced patients, RTX proved to be an effective therapeutic option.

  16. A case of primary ovarian lymphoma with autoimmune hemolytic anemia achieving complete response with Rituximab-based combination chemotherapy

    Directory of Open Access Journals (Sweden)

    N S Ghadyalpatil

    2011-01-01

    Full Text Available Ovarian involvement as primary or secondary lymphomatous process is extremely uncommon. In most cases, the diagnosis is usually not suspected initially and is confirmed only after detailed histopathological evaluation. We report a patient with primary ovarian diffuse large B-cell lymphoma (DLBCL and associated auto-immune hemolytic anemia (AIHA who achieved complete remission after treatment with Rituximab-cyclophosphamide-doxorubicin-vincristine and prednisolone (R-CHOP chemotherapy. This patient was a 50 year old female, who presented with fever, abdominal pain, vomiting, weight loss and anemia. Computed tomography scan of the abdomen and pelvis revealed a large left ovarian mass with bilateral hydronephrosis. We performed exploratory laparotomy and partial resection of the mass was done due to the adhesions. Histopathology confirmed the diagnosis of DLBCL. After six R-CHOP chemotherapy cycles, patient achieved complete response with correction of anemia. To our knowledge, this may be the first case report till date of primary ovarian DLBCL with AIHA treated with R-CHOP chemotherapy who achieved complete remission in terms of primary disease as well as hemolytic anemia.

  17. Long-term results of first salvage treatment in CLL patients treated initially with FCR (fludarabine, cyclophosphamide, rituximab).

    Science.gov (United States)

    Tam, Constantine S; O'Brien, Susan; Plunkett, William; Wierda, William; Ferrajoli, Alessandra; Wang, Xuemei; Do, Kim-Anh; Cortes, Jorge; Khouri, Issa; Kantarjian, Hagop; Lerner, Susan; Keating, Michael J

    2014-11-13

    Although fludarabine, cyclophosphamide, and rituximab (FCR) together are established as a standard first-line treatment of younger patients with chronic lymphocytic leukemia (CLL), there is little information to guide the management of patients with CLL refractory to, or who have relapsed after, receiving frontline FCR treatment. To define optimal salvage strategy and identify patients unsuitable for retreatment with FCR, we examined the survival and treatment outcome of 300 patients enrolled in a phase 2 study of FCR. After a median 142 months of follow-up, 156 patients developed progressive CLL, with a median survival of 51 months after disease progression. The duration of first remission (REM1) was a key determinant of survival after disease progression and first salvage. Patients with a short REM1 (<3 years) had a short survival period, irrespective of salvage therapy received; these patients have high unmet medical needs and are good candidates for investigation of novel therapies. In patients with a long REM1 (≥3 years), salvage treatment with either repeat FCR or lenalidomide-based therapy results in subsequent median survival exceeding 5 years; for these patients, FCR rechallenge represents a reasonable standard of care.

  18. Second cancers in patients with chronic lymphocytic leukemia who received frontline fludarabine, cyclophosphamide and rituximab therapy: distribution and clinical outcomes.

    Science.gov (United States)

    Benjamini, Ohad; Jain, Preetesh; Trinh, Long; Qiao, Wei; Strom, Sara S; Lerner, Susan; Wang, Xuemei; Burger, Jan; Ferrajoli, Alessandra; Kantarjian, Hagop; O'Brien, Susan; Wierda, William; Estrov, Zeev; Keating, Michael

    2015-06-01

    Patients with chronic lymphocytic leukemia (CLL) are known to have an increased incidence of second cancers, but the contribution of commonly used frontline therapies to the incidence of second cancers is unclear. We report on the characteristics, incidence, outcomes and factors associated with second cancers in 234 patients receiving fludarabine, cyclophosphamide and rituximab (FCR) based regimens in the frontline setting. The risk of second cancers was 2.38 times higher than the expected risk in the general population. Ninety-three patients (40%) had other cancers before and 66 patients (28%) after FCR. Rates of therapy related acute myeloid leukemia/myelodysplastic syndrome (t-AML/MDS) (5.1%) and Richter transformation (RT) (9%) were high, while solid tumors were not increased. Overall survival of patients with second cancers after frontline FCR was shorter (median of 4.5 years) compared to patients with and without prior cancers. Second cancer risk after frontline FCR is mainly due to high rates of t-AML/MDS and RT, and as speculated the survival of affected patients is shorter.

  19. Bendamustine and rituximab combination is safe and effective as salvage regimen in Waldenström macroglobulinemia.

    Science.gov (United States)

    Tedeschi, Alessandra; Picardi, Paola; Ferrero, Simone; Benevolo, Giulia; Margiotta Casaluci, Gloria; Varettoni, Marzia; Baratè, Claudia; Motta, Marina; Gini, Guido; Goldaniga, Maria Cecilia; Visco, Carlo; Zaja, Francesco; Belsito Petrizi, Valeria; Ravelli, Erika; Gentile, Massimo; Urbano, Marina Aurora; Franceschetti, Silvia; Ghione, Paola; Orsucci, Lorella; Frustaci, Anna Maria; Gaidano, Gianluca; Vitolo, Umberto; Morra, Enrica

    2015-01-01

    According to the European Society for Medical Oncology and National Comprehensive Cancer Network guidelines on Waldenström macroglobulinemia, bendamustine (B) may be considered a suitable therapeutic option. To address the role of B in combination with rituximab (BR), we analyzed the outcome of 71 patients with relapsed/refractory disease, median age 72 years, treated with R 375 mg/m(2) day 1 and B days 1 and 2 (dosage ranging from 50 to 90 mg/m(2)). Patients had previously received a median number of 2 lines of treatment (range 1-5). Overall and major response rates were 80.2% and 74.6%. Major toxicity was grade 3/4 neutropenia occurring in 13% of courses. There was no significant association between baseline features or patients' characteristics and response achievement. Median progression-free survival was not reached after a median follow-up of 19 months (range 3-54). None of the patients developed aggressive lymphoma or secondary myelodysplastic syndrome/acute myeloid leukemia. BR was found to be an active and well-tolerated salvage regimen leading to rapid disease control.

  20. Combination therapy for rheumatoid arthritis with rituximab and leflunomide(preliminary results of the Russian ARBITR Registry

    Directory of Open Access Journals (Sweden)

    Evgeniy L'vovich Nasonov

    2011-01-01

    Full Text Available The paper analyzes the efficiency and tolerability of a combination of rituximab (RTM and leflunomide (LEF for the treatment of rheumatoid arthritis (RA versus the conventional combination of RTM and methotrexate (MT. The results of 24-week therapy were assessed in the RA patients included into the Russian Biological Therapy Register. A good effect of therapy was achieved in 31.8% of the patients who had received RTM+LEF (p = 0.1. The development of clinical remissions in RA was observed at a practically equal frequency of 13.6 and 11.7%, respectively. The doses of glucocorticoids and nonsteroidal anti-inflammatory drugs used in concurrent anti-inflammatory therapy could be substantially reduced in both groups. In both groups, the rate of side effects was very equal: 21.7% for the RTM+LEF group and 25.7% for the RTM+MT group. Thus, the combination therapy of RTM and LEF in real clinical practice is not considerably different from the most commonly used combination of RMT and MT in efficiency and tolerability and may be successfully used if there are any contraindications to the use of MT.

  1. CHANGES OF BONE MINERAL DENSITY DURING FOUR-YEAR RITUXIMAB AND METHOTREXATE THERAPY IN POSTMENOPAUSAL WOMEN WITH RHEUMATOID ARTHRITIS

    Directory of Open Access Journals (Sweden)

    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.

  2. 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

  3. 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.)

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

    Directory of Open Access Journals (Sweden)

    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.

  5. High titers of anti-HBs prevent rituximab-related viral reactivation in resolved hepatitis B patient with non-Hodgkin's lymphoma.

    Science.gov (United States)

    Cho, Yuri; Yu, Su Jong; Cho, Eun Ju; Lee, Jeong-Hoon; Kim, Tae Min; Heo, Dae Seog; Kim, Yoon Jun; Yoon, Jung-Hwan

    2016-06-01

    Rituximab, an anti-CD20 monoclonal antibody, is associated with an increased risk of hepatitis B virus (HBV) reactivation. This study aimed to determine the predictive factors for rituximab-related HBV reactivation in resolved hepatitis B patients, defined as HBsAg-negative, anti-HBc-positive, and undetectable HBV DNA. Among 840 consecutive patients with CD20-positive B-cell lymphoma who received rituximab-based chemotherapy from 2003 through 2014 at Seoul National University Hospital, 732 patients were excluded because either anti-HBc was not assessed or they were HBsAg-seropositive. This retrospective study included 108 resolved hepatitis B patients. During a median 33.5-month follow-up period, eight cases of HBV reactivation occurred only among the patients with low anti-HBs titers (anti-HBs titers were the protective factors for HBV reactivation (hazard ratio [HR], 0.90 and 0.95, respectively). Among those who did not receive antiviral prophylaxis, patients with high baseline anti-HBs (≥100 mIU/ml) experienced significantly lower risk of HBV reactivation (HR, 0.49; P = 0.006) than the patients with low baseline anti-HBs (anti-HBs titer at baseline and antiviral prophylaxis prevented HBV reactivation, suggesting antiviral prophylaxis should be considered according to baseline anti-HBs titer. Meticulous follow-up for ALT and HBV DNA without antiviral prophylaxis might be possible for the patients with high baseline anti-HBs (≥100 mIU/ml).

  6. 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.

  7. Emergence of long-lived autoreactive plasma cells in the spleen of primary warm auto-immune hemolytic anemia patients treated with rituximab.

    Science.gov (United States)

    Mahévas, Matthieu; Michel, Marc; Vingert, Benoit; Moroch, Julien; Boutboul, David; Audia, Sylvain; Cagnard, Nicolas; Ripa, Julie; Menard, Cédric; Tarte, Karin; Mégret, Jérôme; Le Gallou, Simon; Patin, Pauline; Thai, Lan; Galicier, Lionel; Bonnotte, Bernard; Godeau, Bertrand; Noizat-Pirenne, France; Weill, Jean-Claude; Reynaud, Claude-Agnès

    2015-08-01

    Primary warm autoimmune hemolytic anemia (wAIHA) is a rare autoimmune disease in which red blood cells are eliminated by IgG autoantibodies. We analyzed the antibody-secreting cells in the spleen and the peripheral blood of wAIHA patients in various contexts of treatment. Plasmablasts were observed in peripheral blood of newly diagnosed wAIHA patients and, accordingly, active germinal center reactions were present in the spleen of patients receiving short-term corticosteroid therapy. Long-term corticosteroid regimens markedly reduced this response while splenic plasma cells were able to persist, a fraction of them secreting anti-red blood cell IgG in vitro. In wAIHA patients treated by rituximab and who underwent splenectomy because of treatment failure, plasma cells were still present in the spleen, some of them being autoreactive. By using a set of diagnostic genes that allowed us to assess the plasma cell maturation stage, we observed that these cells displayed a long-lived program, differing from the one of plasma cells from healthy donors or from wAIHA patients with various immunosuppressant treatments, and more similar to the one of normal long-lived bone-marrow plasma cells. Interestingly, an increased level of B-cell activating factor (BAFF) was observed in the supernatant of spleen cell cultures from such rituximab-treated wAIHA patients. These results suggest, in line with our previous report on primary immune thrombocytopenia, that the B-cell depletion induced by rituximab promoted a suitable environment for the maturation and survival of auto-immune long-lived plasma cells in the spleen.

  8. Successful treatment of life-threatening Evans syndrome due to antiphospholipid antibody syndrome by rituximab-based regimen: a case with long-term follow-up.

    Science.gov (United States)

    Rückert, A; Glimm, H; Lübbert, M; Grüllich, C

    2008-08-01

    An association of antiphospholipid antibody syndrome with antibodies directed against either phospholipids or plasma proteins strongly suggest that B-cell dysfunction may be involved in its pathogenesis. Antiphospholipid antibody syndrome with autoimmune cytopenias shows a poor response rate to conventional treatment with anticoagulants, glucocorticosteroids, immunosuppressive agents, intravenous immunoglobulin or plasmapheresis. We report a case of life-threatening antiphospholipid antibody syndrome with Evans syndrome receiving successful multimodal treatment including anti-CD20 monoclonal antibody rituximab with long-term follow-up.

  9. Minimal renal toxicity after Rituximab DHAP with a modified cisplatin application scheme in patients with relapsed or refractory diffuse large B-cell lymphoma

    OpenAIRE

    Lisenko, Katherina; McClanahan, F.; Schöning, Tilman; Schwarzbich, Mark Alexander; Cremer, Martin; Dittrich, Tobias; Ho, Anthony D; Witzens-Harig, Mathias

    2016-01-01

    Background: Rituximab (R) in combination with DHAP is a widely accepted salvage regimen for patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL). A common adverse effect of this protocol is renal toxicity which may result in treatment discontinuation. Assuming that a lower single dose of cisplatin over several days would reduce renal toxicity, our institution has chosen to administer cisplatin in a dosage of 25 mg/m2 per day as a 3-h infusion over 4 consecutive days. M...

  10. Ultrasound-detected joint inflammation and B cell count: related variables for rituximab-treated RA patients?

    Science.gov (United States)

    Valor, Lara; Martínez-Estupiñán, Lina; Janta, Iustina; Nieto, Juan Carlos; Ovalles-Bonilla, Juan Gabriel; González-Fernández, Carlos; Del Rio, Tamara; Hernández-Flórez, Diana; Monteagudo, Indalecio; López-Longo, Francisco Javier; Naredo, Esperanza

    2016-06-01

    This cross-sectional observational study aimed to explore the relationship between B cell count and ultrasound (US)-detected synovitis, in patients with rheumatoid arthritis treated with rituximab. Thirty-seven consecutive RA patients treated with RTX were recruited for the study. The patients underwent clinical [i.e., Disease Activity Score 28 joints (DAS28)], laboratory, and US assessment of 12 joints. Each joint was semiquantitatively (0-3) scored on B-mode and power Doppler mode. The scores were summed, and a global index was created for BM (BMS) and PD scores (PDI) synovitis. BM subclinical synovitis was evident in all patients, with PD synovial signal detected in 16 patients (43.2 %). No correlation was found between DAS28 and US scores. B cells were detected in 27 (72.9 %) patients, but there was no association in the mean B cell count and disease activity as measured by DAS28 (DAS28  2.6 = 49.45, p = 0.52) and PDI score (PDI  1 = 35.44, p = 0.54). There was no correlation between the B cell count and DAS28, BMS, and PDI (r = 0.020, p = 0.907; r = -0.151, p = 0.371; r = -0.099, p = 0.558, respectively). In RTX-treated RA patients, no relationship could be established between US-detected synovitis and peripheral blood B cell count.

  11. ROLE OF MULTIPLEX CYTOKINE ANALYSIS IN THE EVALUATION OF THE EFFICACY OF RITUXIMAB DURING TREATMENT FOR RHEUMATOID ARTHRITIS

    Directory of Open Access Journals (Sweden)

    A. A. Novikov

    2011-01-01

    Full Text Available Along with its basic activity in removing B-lymphocytes, rituximab (RTM causes depletion of a population of CD20+ T cells that can pro- duce a variety of immunoregulatory and proinflammatory cytokines and chemokines. Objective: to define a role of multiplex cytokine analysis in the evaluation of the efficiency of using RMT in rheumatoid arthritis (RA. Subjects and methods. Thirty-four patients with the valid diagnosis of RA according to the ACR criteria of 1987 were examined. The con- centrations of cytokines were measured using the xMAP technology (27-plex. Results and discussion. In the group of patients with a clinical response to therapy with the gene engineering biological agent, there was a decrease in the concentrations of interleukins (IL 1β, 1ra, 2, 4, 6, 9, and 13, granulocyte macrophage colony-stimulating factor (GM- CSF, γ-interferon (IFN-γ, monocyte chemoattractant 1 at week 8 of therapy; that in IL 1β, 1ra, 2, 5, 6, 9, 10, 12, 13, and 15, fibroblast growth factor 2 (FGF-2, GM-CSF, IFN-γ, and tumor necrosis factor-α at week 24, and that in IL-9 at week 40. The no-clinical response group showed a reduction in GM-CSF at week 8 and in IL-2 and macrophage inflammatory protein 1β (MIP-1β at week 40, and an increase in IL-8 at week 8. At week 8 after drug infusion, the elevated levels of IL-17 and MIP-1β can be identified as possible early pre- dictors of a response (at week 40. Comparison of the baseline cytokine levels in the groups with different clinical response demonstrated a more than three-fold increase in the concentrations of IL 4, 5, 7, 8, 10, 12, 13, 15, 17, IFN-γ, and vascular endothelial growth factor, and IL-8 at weeks 8 and 40, respectively. 

  12. 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

    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.......86), respectively. The human equivalents of highest dose organs with and without pre-dose are osteogenic cells at 30.8¿±¿0.4 µSv/MBq and the spleen at 99¿±¿4 µSv/MBq, respectively. CONCLUSIONS: PET imaging with PETRIT in huCD20 transgenic mice provided human dosimetry data for eventual applications in non......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...

  13. Central nervous system involvement in diffuse large B-cell lymphoma: an analysis of risks and prevention strategies in the post-rituximab era.

    Science.gov (United States)

    Fletcher, Christopher D; Kahl, Brad S

    2014-10-01

    Central nervous system (CNS) relapse in patients with diffuse large B-cell lymphoma (DLBCL) occurs infrequently (approximately 5%), but is almost universally fatal. Controversy exists regarding which factors most reliably identify high risk patients in the post-rituximab era. Clarification is also needed regarding the value of prophylaxis strategies when contemporary rituximab-based chemotherapy regimens (chemoimmunotherapy) are used. A systematic review with focus on the era of chemoimmunotherapy has been performed. Involvement of > 1 extranodal site plus an elevated lactate dehydrogenase level identifies individuals at highest risk (> 20%) for CNS recurrence who merit additional evaluation. Only certain solitary extranodal sites (testis, kidney and breast, but not bones, orbit or epidural space) appear to confer higher risk in patients receiving chemoimmunotherapy. Data from studies employing modern regimens suggest that intrathecal prophylaxis is ineffective even for high risk populations. Systemic prophylaxis (e.g. high dose methotrexate) may be useful, but does not have strong support in the literature. A significant portion of patients with high risk features (˜25%) may already have subclinical CNS disease, which requires alternative detection and treatment strategies. Flow cytometry is a promising approach with increased sensitivity. Widespread use of this approach could redefine what risk and prophylaxis mean. An algorithm for incorporating risk factors, evaluation and treatment is presented.

  14. Rituximab Improves Subclinical Temporal Dispersion of Distal Compound Muscle Action Potential in Anti-MAG/SGPG Neuropathy Associated with Waldenström Macroglobulinemia: A Case Report

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    Kanji Yamamoto

    2013-02-01

    Full Text Available Patients with anti-myelin-associated glycoprotein (MAG/sulfated glucuronyl paragloboside (SGPG neuropathy associated with Waldenström macroglobulinemia show demyelinating neuropathy, but the temporal dispersion of distal compound muscle action potential (CMAP in motor nerve conduction studies (NCS, which represents heterogeneous demyelination at the motor nerve terminal, is rare. We report on a 70-year-old man with anti-MAG/SGPG neuropathy associated with Waldenström macroglobulinemia; he had a 2-year history of mild dysesthesia of the foot sole without any motor symptoms. He showed marked temporal dispersion of distal CMAP in the tibial nerve with other demyelinating findings in the NCS. The temporal dispersion of distal CMAP in the tibial nerve improved significantly, and motor function was again normal 1 year after rituximab monotherapy. The temporal dispersion of distal CMAP in anti-MAG/SGPG neuropathy is rare, but it could occur from an early stage when the patients show mild or no motor symptoms. Rituximab therapy before secondary axonal degeneration has great potential to reverse the effects of the demyelination including the temporal dispersion of distal CMAP, and to prevent the deterioration of neuropathy in anti-MAG/SGPG neuropathy.

  15. Cold Autoimmune Hemolytic Anemia due to High-grade non Hodgkin's B cell Lymphoma with Weak Response to Rituximab and Chemotherapy Regimens.

    Science.gov (United States)

    Nazel Khosroshahi, Behzad; Jafari, Mohammad; Vazini, Hossein; Ahmadi, Alireza; Shams, Keivan; Kholoujini, Mahdi

    2015-07-01

    Autoimmune hemolytic anemia (AIHA) is characterized by shortening of red blood cell (RBC) survival and the presence of autoantibodies directed against autologous RBCs. Approximately 20% of autoimmune hemolytic anemia cases are associated with cold-reactive antibody. About half of patients with AIHA have no underlying associated disease; these cases are termed primary or idiopathic. Secondary cases are associated with underlying diseases or with certain drugs. We report herein a rare case of cold autoimmiune hemolytic anemia due to high-grade non-Hodgkin's lymphoma of B-cell type with weak response to rituximab and chemotherapy regimens. For treatment B cell lymphoma, Due to lack of treatment response, we used chemotherapy regimens including R- CHOP for the first time, and then Hyper CVAD, R- ICE and ESHAP were administered, respectively. For treatment of autoimmune hemolytic anemia, we have used the corticosteroid, rituximab, plasmapheresis and blood transfusion and splenectomy. In spite of all attempts, the patient died of anemia and aggressive lymphoma nine months after diagnosis. To our knowledge, this is a rare report from cold autoimmune hemolytic anemia in combination with high-grade non-Hodgkin's lymphoma of B-cell type that is refractory to conventional therapies.

  16. Evaluation of the Rituximab Maintenance Improves Clinical Outcome of Relapsed/Resistant Follicular Non Hodgkin's Lymphoma, Both in Patients with and without Rituximab during Induction: Results of A Prospective Randomized Phase Ⅲ Intergroup Trial%无论诱导阶段是否曾使用过利妥昔单抗维持治疗均可改善复发/难治滤泡性淋巴瘤临床预后Ⅲ期随机对照研究的评价

    Institute of Scientific and Technical Information of China (English)

    夏忠军; 李文瑜

    2007-01-01

    @@ 1 文献类型 治疗. 2 证据水平 1b. 3 文献来源 Oers MHJ, Klasa R, Marcus RE, et al.Rituximab maintenance improves clinical outcome of relapsed/resistant follicular non-Hodgkin's lymphoma,both in patients with and without rituximab during induction: results of a prospective randomized phase Ⅲ intergroup trial [J]. Blood, 2006,108(10):3295-3301.

  17. Primary therapy of Waldenström macroglobulinemia (WM) with weekly bortezomib, low-dose dexamethasone, and rituximab (BDR): Long-term results of a phase 2 study of the European Myeloma Network (EMN)

    NARCIS (Netherlands)

    M.A. Dimopoulos (Meletios); R. Garcia-Sanz (Ramon); M. Gavriatopoulou (Maria); P. Morel; M.-C. Kyrtsonis (Marie-Christine); L.K. Michalis (Lampros); Z. Kartasis (Zafiris); X. Leleu; G. Palladini (Giovanni); A. Tedeschi (Alessandra); D. Gika (Dimitra); G. Merlini; E. Kastritis (Efstathios); P. Sonneveld (Pieter)

    2013-01-01

    textabstractIn this phase 2 multicenter trial, we evaluated the activity of bortezomib, dexamethasone, and rituximab (BDR) combination in previously untreated symptomatic patients with Waldenström macroglobulinemia (WM). To prevent immunoglobulin M (IgM) "flare," single agent bortezomib (1.3 mg/m 2

  18. Research advances of rituximab resistance in B-cell non-Hodgkin lymphoma%利妥昔单抗治疗B细胞非霍奇金淋巴瘤的耐药机制研究进展

    Institute of Scientific and Technical Information of China (English)

    吴剑秋

    2013-01-01

    Anti-CD20 monoclonal antibody rituximab has become an essential component of treatment regimens for B-cell non-Hodgkin lymphoma(NHL).It is routinely incorporated into all phases of conventional treatment of B-cell NHL,but the precise mechanisms of action of rituximab in human remain unknown.This article will clarify the mechanisms of action of rituximab,the incidence and potential mechanisms of resistance.Finally,the novel approaches to modulate the antibody,the tumor cell,and the host immunologic environment to overcome rituximab resistance are discussed.%抗CD20单克隆抗体利妥昔单抗已经成为治疗B细胞非霍奇金淋巴瘤(NHL)的重要组成部分.尽管临床应用广泛,但肿瘤细胞对利妥昔单抗的耐药机制尚不明确.文章阐述了利妥昔单抗的作用机制、耐药的发生以及潜在的耐药机制,并对调节抗体、肿瘤细胞和宿主的免疫状况等克服耐药的方法进行了探讨.

  19. Treatment with rituximab, cyclophosphamide, doxorubicin, vincristine and prednisolone is beneficial but toxic in very elderly patients with diffuse large B-cell lymphoma : a population-based cohort study on treatment, toxicity and outcome

    NARCIS (Netherlands)

    Boslooper, Karin; Kibbelaar, Robby; Storm, Huib; Veeger, Nic J. G. M.; Hovenga, Sjoerd; Woolthuis, Gerhard; van Rees, Bas; de Graaf, Elly; van Roon, Eric; Kluin-Nelemans, Hanneke C.; Joosten, Peter; Hoogendoorn, Mels

    2014-01-01

    To assess treatment strategies, toxicity and outcome in very elderly patients (aged >= 75 years) diagnosed with diffuse large B-cell lymphoma (DLBCL) in the rituximab era, an observational population-based cohort study was performed. From 103 patients with a median age of 81 years, data of clinical

  20. Comparison of the efficacy and safety of Rituximab (Mabthera™ and its biosimilar (Reditux™ in diffuse large B-cell lymphoma patients treated with chemo-immunotherapy: A retrospective analysis

    Directory of Open Access Journals (Sweden)

    Partha Sarathi Roy

    2013-01-01

    Full Text Available Background: Rituximab (Mabthera™ have been in use in India since 2000. A biosimilar molecule of rituximab (Reditux™ was approved in India in 2007. This retrospective audit was done to compare the efficacy and safety of Mabthera™ with Reditux™. Materials and Methods: We reviewed the charts of 223 adult diffuse large B-cell lymphoma patients who had received cyclophosphamide, doxorubicin, vincristine and prednisolone with rituximab chemotherapy. Tumor recurrence, survival and toxicities experienced during chemotherapy were obtained from the patient charts. The survival analysis was restricted to patients who received at least 4 cycles of the same brand. Results: Of the 223 patients evaluated, 101 received Mabthera™, 72 received Reditux™. There were no differences in the infusional reaction rates, grades 3 and 4 neutropenia and oral mucositis between the two brands. Complete-remission (CR rates were similar with Mabthera™ and Reditux™ (75% and 82%, respectively; P = 0.294. The progression free survival (PFS rate at 5 years were 72% in Mabthera™ and 81% in Reditux™ (P = 0.382. The overall survival (OS at 5 years were comparable in the two groups (66% in Mabthera™ and 76% in Reditux™; P = 0.264. Conclusion: We observed no significant differences in the toxicity, tumor response rates, PFS and OS between the two available brands of rituximab.

  1. Long-Term Remission of Primary Bone Marrow Diffuse Large B-Cell Lymphoma Treated with High-Dose Chemotherapy Rescued by In Vivo Rituximab-Purged Autologous Stem Cells

    Directory of Open Access Journals (Sweden)

    Hiroshi Kazama

    2012-01-01

    Full Text Available Primary bone marrow diffuse large B-cell lymphoma (DLBCL is a rare type of extranodal lymphoma with poor prognosis. Here, we report a case of primary bone marrow DLBCL successfully treated with high-dose chemotherapy and rescued by in vivo rituximab-purged autologous stem cells. A 39-year-old woman visited our hospital because of anemia. Bone marrow examination revealed a large B-cell lymphoma invasion. An 18F-fluorodeoxyglucose positron emission tomography scan revealed disseminated bone marrow uptake without evidence of dissemination at other sites. These findings led to a diagnosis of primary bone marrow DLBCL. Our patient underwent R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone chemotherapy and achieved complete remission. Subsequently, she received high-dose chemotherapy with an in vivo rituximab-purged autologous stem cell transplant. Seven years have passed since the transplantation, and she remains in remission. This suggests that transplantation of an in vivo rituximab-purged autograft is a promising strategy for primary bone marrow DLBCL.

  2. Simultaneous Assessment of Rotavirus-Specific Memory B Cells and Serological Memory after B Cell Depletion Therapy with Rituximab

    Science.gov (United States)

    Herrera, Daniel; Rojas, Olga L.; Duarte-Rey, Carolina; Mantilla, Rubén D.; Ángel, Juana; Franco, Manuel A.

    2014-01-01

    The mechanisms that contribute to the maintenance of serological memory are still unclear. Rotavirus (RV) memory B cells (mBc) are enriched in IgM+ and CD27- subpopulations, which are associated with autoimmune diseases pathogenesis. In patients with autoimmune diseases treated with Rituximab (RTX), some autoantibodies (auto-Abs) decrease after treatment, but other auto-Abs and pathogen-specific IgG Abs remain unchanged. Thus, maintenance of autoimmune and pathogen-specific serological memory may depend on the type of antigen and/or Ab isotype evaluated. Antigen-specific mBc and antigen-specific Abs of different isotypes have not been simultaneously assessed in patients after RTX treatment. To study the relationship between mBc subpopulations and serological memory we characterized total, RV- and tetanus toxoid (TT)-specific mBc by flow cytometry in patients with autoimmune diseases before and after treatment with RTX. We also measured total, RV- and TT-Abs, and some auto-Abs by kinetic nephelometry, ELISA, and EliA tests, respectively. Minor differences were observed between the relative frequencies of RV-mBc in healthy controls and patients with autoimmune disease. After RTX treatment, naïve Bc and total, RV- and TT-specific mBc [IgM+, switched (IgA+/IgG+), IgM+ only, IgD+ only, and CD27- (IgA+/IgG+/IgM+)] were significantly diminished. An important decrease in total plasma IgM and minor decreases in total IgG and IgA levels were also observed. IgM rheumatoid factor, IgG anti-CCP, and IgG anti-dsDNA were significantly diminished. In contrast, RV-IgA, RV-IgG and RV-IgG1, and TT-IgG titers remained stable. In conclusion, in patients with autoimmunity, serological memory against RV and TT seem to be maintained by long-lived plasma cells, unaffected by RTX, and an important proportion of total IgM and serological memory against some auto-antigens seem to be maintained by short-lived plasma cells, dependent on mBc precursors depleted by RTX. PMID:24819618

  3. Impact of rituximab on immunoglobulin concentrations and B cell numbers after cyclophosphamide treatment in patients with ANCA-associated vasculitides.

    Directory of Open Access Journals (Sweden)

    Nils Venhoff

    Full Text Available OBJECTIVE: To assess the impact of immunosuppressive therapy with cyclophosphamide (CYC and rituximab (RTX on serum immunoglobulin (Ig concentrations and B lymphocyte counts in patients with ANCA-associated vasculitides (AAVs. METHODS: Retrospective analysis of Ig concentrations and peripheral B cell counts in 55 AAV patients. RESULTS: CYC treatment resulted in a decrease in Ig levels (median; interquartile range IQR from IgG 12.8 g/L (8.15-15.45 to 9.17 g/L (8.04-9.90 (p = 0.002, IgM 1.05 g/L (0.70-1.41 to 0.83 g/L (0.60-1.17 (p = 0.046 and IgA 2.58 g/L (1.71-3.48 to 1.58 g/L (1-31-2.39 (p = 0.056 at a median follow-up time of 4 months. IgG remained significantly below the initial value at 14.5 months and 30 months analyses. Subsequent RTX treatment in patients that had previously received CYC resulted in a further decline in Ig levels from pre RTX IgG 9.84 g/L (8.71-11.60 to 7.11 g/L (5.75-8.77; p = 0.007, from pre RTX IgM 0.84 g/L (0.63-1.18 to 0.35 g/L (0.23-0.48; p<0.001 and from pre RTX IgA 2.03 g/L (1.37-2.50 to IgA 1.62 g/L (IQR 0.84-2.43; p = 0.365 14 months after RTX. Treatment with RTX induced a complete depletion of B cells in all patients. After a median observation time of 20 months median B lymphocyte counts remained severely suppressed (4 B-cells/µl, 1.25-9.5, p<0.001. Seven patients (21% that had been treated with CYC followed by RTX were started on Ig replacement because of severe bronchopulmonary infections and serum IgG concentrations below 5 g/L. CONCLUSIONS: In patients with AAVs, treatment with CYC leads to a decline in immunoglobulin concentrations. A subsequent RTX therapy aggravates the decline in serum immunoglobulin concentrations and results in a profoundly delayed B cell repopulation. Surveying patients with AAVs post CYC and RTX treatment for serum immunoglobulin concentrations and persisting hypogammaglobulinemia is warranted.

  4. Radiation Therapy in Primary Mediastinal B-Cell Lymphoma With Positron Emission Tomography Positivity After Rituximab Chemotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Filippi, Andrea Riccardo, E-mail: andreariccardo.filippi@unito.it [Department of Oncology, University of Torino, Torino (Italy); Piva, Cristina [Department of Oncology, University of Torino, Torino (Italy); Giunta, Francesca; Bellò, Marilena [Nuclear Medicine, Città della Salute e della Scienza, Torino (Italy); Chiappella, Annalisa; Caracciolo, Daniele [Hematology, Città della Salute e della Scienza, Torino (Italy); Zotta, Michela [Department of Medical Sciences, University of Torino, Torino (Italy); Douroukas, Anastasios [Positron Emission Tomography Center IRMET, Torino (Italy); Ragona, Riccardo [Department of Oncology, University of Torino, Torino (Italy); Vitolo, Umberto [Hematology, Città della Salute e della Scienza, Torino (Italy); Bisi, Gianni [Department of Medical Sciences, University of Torino, Torino (Italy); Ricardi, Umberto [Department of Oncology, University of Torino, Torino (Italy)

    2013-10-01

    Purpose: To investigate the role of radiation therapy (RT) in patients affected with primary mediastinal B-cell lymphoma (PMBCL) with residual {sup 18}fluorodeoxyglucose positron emission tomography ({sup 18}FDG-PET)-positive disease after rituximab chemotherapy (R-CT). Methods and Materials: Thirty-seven patients treated with R-CT and RT, all with {sup 18}FDG-PET scan at diagnosis and before RT, were included. All {sup 18}FDG-PET scans were reviewed, and responses were classified according to the Deauville 5-point scoring system. Outcomes measures were overall survival (OS) and progression-free survival (PFS), estimated for the whole cohort and for subgroups according to {sup 18}FDG-PET score after R-CT. Results: The median follow-up time was 40.9 months. Three patients were assigned to Deauville score 1 (8.1%), 9 to score 2 (24.3%), 7 to score 3 (19%), 14 to score 4 (37.8%), and 4 to score 5 (10.8%). After RT, all patients with score 3-4 experienced a complete response (CR). Among patients with score 5, 1 was in CR (25%), 2 had persistent positivity (50%), and 1 showed progressive disease (25%). A total of 4 patients experienced progression or relapse: 1 of 33 (3%) with scores 1-4, and 3 of 4 (75%) with score 5. The 3-year OS and PFS of the whole cohort were 89.8% and 88.7%, respectively. OS was significantly different between scores 1-3 and scores 4-5 (100% vs 77% at 3 years, P<.05). Patients with a score of 5 had a significantly worse outcome than did all other patients (OS at 2 years, 33.3% vs 100%). Conclusions: Approximately 50% of PMBCL patients show residual disease at {sup 18}FDG-PET scan after R-CT. RT is able to convert to CR approximately 85% of these patients, but those with a Deauville score of 5 (10%) appear at high risk of progression and death, and they might be candidates for intensified programs.

  5. THE RESULTS OF A PHASE III COMPARATIVE CLINICAL TRIAL OF RITUXIMAB (ACELLBIA® AND MABTHERA® IN RHEUMATOID ARTHRITIS (THE BIORA STUDY

    Directory of Open Access Journals (Sweden)

    E. L. Nasonov

    2016-01-01

    Full Text Available The article considers the results of an international multicenter randomized clinical trial of the efficacy and safety of the brand-name drug rituximab (MabThera, a monoclonal antibody against CD20 antigen of B cells, and its biosimi-lar drug (Acellbia® (the BIORA study in patients with rheumatoid arthritis (RA refractory to therapy with tumor necrosis factor-а inhibitors.Objective: to provide evidence for the therapeutic equivalence of Acellbia® and MabThera® and also to assess their interchangeability.Subjects and methods. The trial enrolled adult patients with active seropositive RA, who were randomized into two groups (1:1: 1 the patients who received Acellbia® 1000 mg intravenously on days 1 and 15; 2 those who had MabThera® in a similar way. When RA activity persisted at 24 weeks, there was re-randomization (1:1 with a partial overlap: Group 1 patients were randomized into group AA (the drug of the second therapy cycle was Acellbia® or Group AM (that was MabThera®, the similar methodology was followed in Group 2 (Groups MM and MA. Throughout the study, the patients received methotrexate at a stable dose of 7.5—25 mg/week and folic acid at a dose of 5 mg/week. The follow-up lasted 48 weeks.Results and discussion. 24 weeks after treatment initiation, the ACR20 response was observed in 84.1% of the patients in the Acellbia® group (95% CI, 74.75—90.50 and in 87% in the MabThera® group (95% CI, 77.71—92.79%; p = 0.773, which suggests that the drugs are therapeutically equivalent. In the second phase of the study, the efficiency of therapy remained high; there were no differences in Groups AA/MM, AA/AM and MM/MA. In both phases, the safety profile of the drugs was comparable; the immunogenicity of treatment remained low. The findings suggest that the brand-name MabThera® and its biosimilar drug Acellbia® are equivalent. Switching from the biosimilar drug to the brand-name one and vice versa has no negative impact on treatment

  6. A clinical study on the therapeutic effect of rituximab in combination with autologous peripheral blood stem cell transplantation in treatment of CD20+ B cellulous non-Hodgkin lymphoma

    Directory of Open Access Journals (Sweden)

    Yong-sheng CHEN

    2013-07-01

    Full Text Available Objective To investigate the therapeutic effect of autologous peripheral blood stem cell transplantation (APBSCT in combination with rituximab in treatment of CD20+ B cellulous non-Hodgkin's lymphoma (B-NHL. Methods Sixty patients with CD20+ aggressive or refractory and recurrent B-NHL and treated with APBSCT in our department from Jan. 2005 to Jan. 2011 were admitted. All the subjects were divided into 2 groups according to their own choice: 25 patients received rituximab treatment (treatment group and 35 patients were treated without rituximab treatment (control group. All patients underwent chemotherapy and APBSCT. For patients in treatment group, rituximab was used with CHOP before collecting the stem cells and after the transplantation. After transplantation, rituximab and IL-2 were used in treatment group every 3-6 months as maintenance treatment. Results No side effect was observed during the use of rituximab either before or after transplantation. The mononuclear cell count in treatment and control group was (8.2±2.9×108/kg and (8.4±3.9×108/kg (P=0.822, respectively; CD34+cell count was (12.3±12.7×106/kg and (13.2±13.9×106/kg (P=0.799, respectively. Haemopoiesis reconstruction was successfully achieved in the patients of treatment group, while 3 patients in control group failed to have haemopoiesis reconstruction. No significant difference was found between two groups on the recovery time of neutrophilic granulocytes and platelets. All patients achieved complete remission. The average follow-up time was 22 months. The disease relapsed in two patients in treatment group and six in control group. The 3-year overall survival rate in treatment group (91.6% was a little higher than that in control group (69.5%, P=0.060. Conclusion To patients of CD20+ B lymphoma, the use of rituximab shows no side effect before or after collection of stem cell and hemopoiesis reconstruction, and the overall survival rate may be improved.

  7. Livedo reticular associado com Anemia Hemolítica Autoimune: remissão prolongada induzida pelo Transplante de Células-Tronco do Sangue Periférico com recaída após 10 anos e restauração dos níveis de hemoglobina por rituximabe Livedo reticularis associated with autoimmune hemolytic anemia: prolonged remission induced by peripheral blood stem cell transplantation relapse after 10 years and restoration of hemoglobin levels by rituximab

    Directory of Open Access Journals (Sweden)

    Eurípedes Ferreira

    2012-02-01

    Full Text Available A anemia hemolítica autoimune (AHAI é uma doença na qual são produzidos anticorpos diretamente contra as glicoproteínas adsorvidas na superfície da membrana dos eritrócitos. Algumas medicações e outras associações têm sido implicadas. Descrevemos e discutimos um caso de livedo reticular associado à AHAI tratado com transplante de células-tronco de sangue periférico (TCTSP e que entrou em total remissão por 10 anos. Após esse período, a paciente apresentou recaída, foi tratada com anticorpo anti-CD20 (rituximabe, e atualmente encontra-se em total remissão. O papel do TCTSP e o uso de rituximabe no tratamento de AHAI serão discutidos neste relato de casoAutoimmune hemolytic anemia (AIHA is a disease where patients produce antibodies against erythrocytes directed towards membrane glycoproteins adsorbed onto the erythrocyte surface. Drugs and other associations have been implicated. It is described and discussed a case of livedo reticularis associated with AIHA treated with peripheral blood stem cell transplantation (PBSCT that went into full remission for 10 years. After that period the patient relapsed and was treated with antibody anti-CD20, rituximab, and is now in full remission. The role of PBSCT and rituximab in the treatment of AIHA will be discussed

  8. Thyrotoxicosis due to functioning metastatic follicular thyroid carcinoma after twelve I-131 therapies.

    Science.gov (United States)

    Tan, Jian; Zhang, Guizhi; Xu, Wengui; Meng, Zhaowei; Dong, Feng; Zhang, Fuhai; Jia, Qiang; Liu, Xuehui

    2009-09-01

    We present a case of functioning metastatic follicular thyroid carcinoma (FTC) causing severe thyrotoxicosis despite four years 12 iodine-131 therapies (1.461 Ci cumulatively). Initially, the patient had ostalgia and fracture in the right femur. Surgery-confirmed metastatic bone FTC and thyroidectomy-confirmed FTC. One month later, iodine-131 treatment commenced. During the follow-up, different metastatic sites showed different outcomes. Lung metastases disappeared, a thigh metastasis persisted, a new metastasis in the head occurred and pelvic metastases deteriorated into a huge mass elevating thyroglobulin and causing thyrotoxicosis within 3 months. Presurgical PET/CT also demonstrated the massiveness of the pelvic metastases. Thyrotoxicosis disappeared after surgical removal of the pelvic lesion.

  9. An experiment to use medical I-131 as tracer in a city sewer system

    Energy Technology Data Exchange (ETDEWEB)

    Ulbrich, Susanne; Fischer, Helmut W. [University of Bremen, Institute of Environmental Physics, Otto-Hahn-Allee 1, D-28359 Bremen (Germany)

    2014-07-01

    City sewer systems have to reliably carry residential and industrial wastewater to treatment plants, often mixed with rainwater. Transport in the sewer system is regularly modelled in order to predict sewerage levels, transport velocities and volume discharges. Radioisotopes would be interesting tracers, as they can be detected quickly and without the need of applying wet chemistry. Medical isotopes are released in large quantities (many MBq) by excretion from patients either at the location of administration or from elsewhere, most probably the patient's home. Depending on diagnostic or treatment modality, isotopes of different physical characteristics are used, often bound to compounds of specific metabolic behaviour. Routine environmental surveillance regularly detects the most common diagnostic ({sup 99m}Tc) and therapeutic ({sup 131}I) isotopes in city wastewater samples. Except for {sup 131}I in the case of a nuclear emergency, no contributions from sources other than medical are expected. Medical isotopes therefore might be used for tracing purposes, provided individual inputs can be identified and separated. A field experiment has been designed involving {sup 131}I releases from a single patient who had undergone radioiodine thyroid ablation therapy. This modality is applied after thyroid cancer surgery in order to destroy residual thyroid tissue. Activities up to 5 GBq of {sup 131}I are used which are excreted within few days, as no iodine-retaining thyroid tissue remains. In Germany, about 20,000 of these treatments are performed yearly. For a sewer system of 500,000 inhabitants, about 150 cases would be expected per year, making it quite improbable to have interference between individual patient releases in the same region of the city sewer system. Practically, the radiometric laboratory was informed of the expected release of an (anonymous) patient from the collaborating radiotherapy unit several days in advance, plus the approximate location of the patient's home. Together with the sewage system authority, automated sampling (mostly in 6 h intervals) over one week at four locations between the patient's home quarter and the sewage plant inlet was planned and successfully conducted, delivering a total of 84 samples. Sampling started before the assumed arrival of the patient at his home, to account for 'background' signal due to releases from other patients. The samples were investigated for {sup 131}I by high resolution gamma spectroscopy, with a detection threshold of down to ca. 0.1 Bq/l, depending on the allocated measurement time. Data time series plots show clearly distinguishable peaks in {sup 131}I activity, with peak amplitude decreasing from over 1 kBq/l to below 1 Bq/l with distance from the patient's home quarter (due to dilution) and peak time being retarded (due to transport time). At the two most distant sampling points, the peak appears on a variable background, attributed to {sup 131}I releases of other patients. Modelling with specific sewer system software is still under way, but the data already show that under suitable conditions medical isotopes can successfully be used as sewage tracers. (authors)

  10. Marcación de fibrinógeno con I-131

    OpenAIRE

    Seminario, Conrado; Capillo, Teobaldo; Montañez, José

    1983-01-01

    De las diferentes técnicas de marcación radioactiva del fibrinogeno humano liofilizado, se ha seleccionado la del monocloruro de Iodo modificada. La marcación de la molécula se efectuó en medio alcalino de buffler glicina en el que se hace actuar la solución de Iodo estable y luego del isótopo radiactivo. Los procesos de marcación efectuados con actividades variables tuvieron un rendimiento superior al 40 %, la purificación realizada con resina amberlita no permitió en ningún caso impurezas m...

  11. Iodine I-131 With or Without Selumetinib in Treating Patients With Recurrent or Metastatic Thyroid Cancer

    Science.gov (United States)

    2017-01-26

    Poorly Differentiated Thyroid Gland Carcinoma; Recurrent Thyroid Gland Carcinoma; Stage IVA Thyroid Gland Follicular Carcinoma; Stage IVA Thyroid Gland Papillary Carcinoma; Stage IVB Thyroid Gland Follicular Carcinoma; Stage IVB Thyroid Gland Papillary Carcinoma; Stage IVC Thyroid Gland Follicular Carcinoma; Stage IVC Thyroid Gland Papillary Carcinoma

  12. [Blocking of the thyroid against I-131 following a nuclear disaster].

    Science.gov (United States)

    Kroizman-Sheiner, Einat; Brickner, Dov; Canfi, Ayala; Schwarzfuchs, Dan

    2005-07-01

    The Chernobyl accident, the recent terrorists' attacks and constant threats, have all once again evoked the fear of a nuclear disaster, in Israel and worldwide. Iodine-131 is a major fission product of nuclear reactors and is highly likely to be released into the atmosphere in severe nuclear disasters. The radioiodine is released as a gas, easily spreads over large areas and is easily absorbed via the respiratory system. Iodine-131 emits gamma and beta radiation in high energies, and is readily absorbed by the thyroid which is a target organ for iodine. The resulting exposure to the thyroid might be very high. A sharp increase in thyroid cancer incidence in children was observed following the Chernobyl accident. This article reviews the medical knowledge about strategies and medications aimed at minimizing the absorption of radioiodine into the thyroid. In addition to regular safety means such as sheltering, restriction of locally produced food products and relocation of the population, the best prophylaxis against thyroid exposure is overloading the gland with stable iodine (as potassium iodide), as soon as possible. Recently, the Israeli government decided to distribute Potassium Iodide tablets to the population in the vicinity of the two nuclear research centers in the country. When this treatment is contraindicated, iodine free thionamides or potassium perchlorate are suggested.

  13. I-131-treatment of non-toxic goitre. Radiojodtherapie der Struma mit Euthyreose

    Energy Technology Data Exchange (ETDEWEB)

    Leisner, B.; Grotefendt, M. (Allgemeines Krankenhaus St. Georg, Hamburg (Germany, F.R.). Abt. fuer Nuklearmedizin)

    1990-12-01

    Radioiodine is a safe and effective treatment of thyroid enlargement with or - in the presence of significant amounts of autonomously functioning tissue - without true euthyroidism. The indications are esentially the same as for surgery, except the case of a goitre recidive and of recurrent nerve injury, for which radioiodine is the treatment of choise. On the contrary, large cold nodules and a suspicion of malignancy preclude it. The size reduction of about 40% is less than that obtained by surgery, but there are no side effects and no recurrences. Hypothyroidism occurs in 4% of the cases. Unfortunately, the number of specially equipped institutions that are allowed to perform radioiodine therapy is yet restricted. (orig.).

  14. 77 FR 71432 - Agency Information Collection Activities: Application for Travel Document, Form Number I-131...

    Science.gov (United States)

    2012-11-30

    ... of the Form/Collection: Application for Travel Document. (3) Agency form number, if any, and the... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF HOMELAND SECURITY U.S. Citizenship and Immigration Services Agency Information Collection Activities:...

  15. Use of I-131- CRTX for targeting malignant adenocarcinoma in mice: biodistribution and radiation dosimetry

    Energy Technology Data Exchange (ETDEWEB)

    Santos, Raquel Gouvea dos; Soares, Marcella Araugio; Andrade, Henrique Martins de, E-mail: santosr@cdtn.br [Centro de Desenvolvimento da Tecnologia Nuclear (CDTN/CNEN-MG), Belo Horizonte, MG (Brazil); Santos, Marcos Antonio da Cunha [Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, MG (Brazil). Departamento de Estatistica

    2008-07-01

    Snake venoms molecules have been shown to play a role not only in the survival and proliferation of tumour cells but also in the processes of tumour cell adhesion, migration and angiogenesis. We have shown that {sup 125}I-Crtx, a radiolabeled version of a protein derived from Crotalus durissus terrificus snake venom (Cdt), specifically binds to tumor and triggers apoptotic death. This study reports the biokinetic profile of {sup 99m}Tc-Cdt and {sup 125/131}I-Crtx in Swiss mice bearing Ehrlich solid tumor and MIRD formulation was applied to calculate the absorbed radiation doses for various organs and tumor site. Biokinetic evaluations were performed up to 24 h after intravenous (i.v) or intratumor (i.tu.) injection of {sup 99m}Tc-Cdt or {sup 125/131}I-Crtx. Time-activity curves were generated for the main organs by fitting the organ specific mass mean counts. The radiation dose from {sup 131}I-Crtx was calculated based on non penetrating radiation in the mouse model. Biokinetics data from {sup 99m}Tc-Cdt after i.v. injection in mice tumor model showed rapid blood clearance (T{sub 1/2}= 36.1 ± 2.4 min.), slow tumor clearance (T{sub 1/2}: 108.3 ± 19.5 min.) and indicated the kidneys as the main excretion pathway. Interaction studies in vitro demonstrated that {sup 125}I-Crtx recognize specific sites on Erlich tumor cell membrane. Upon intravenous and intratumor administration of {sup 131}I-Crtx in mice bearing Erlich tumor, it was observed high uptake in tumor site in vivo (Ã =72kBq x h/g) resulting in a high absorbed dose radiation to tumor site. Distributions of {sup 125/131}I-Crtx i.v. were only significant in tumor, stomach, liver and kidneys, reflecting non-specific uptake of Crtx in normal excretion tissues in vivo. Intratumoral administration reduced significantly the radiation dose to the kidneys (42-fold lower) and increased the uptake by the tumor site (128- fold higher). {sup 131}I control was run in a parallel experiment and showed no significant tumor uptake. In conclusion, {sup 131}I-Crtx had a high concentration in tumor and low concentration in normal organs in mice bearing Erlich tumor. Tumor-to-normal tissue radiation dose ratio, for intratumor injected {sup 131}I-Crtx, were more than 60-fold higher depending on the organ. Our results indicate that Cdt components may provide interesting templates for development of a tool for targeted radiotherapy against adenocarcinoma. (author)

  16. Demonstration by radionuclide imaging of possible vascular steal from a renal transplant. [I-131, Tc-99

    Energy Technology Data Exchange (ETDEWEB)

    Bloss, R.S.; McConnell, R.W.; McConnell, B.G.; Floyd, M.; Conner, W.T.; Henry, R.G.; Kahan, B.D.

    1979-10-01

    Radionuclide studies in a renal-transplant patient with congestive heart failure suggested vascular steal from the renal allograft by a contralateral femoral arteriovenous fistula. These reliable, noninvasive diagnostic procedures have potential use in similar settings to evaluate allograft perfusion and function. Correction by removal of the fistula was demonstrated.

  17. Control study between Rituximab single use and Rituximab combined with rhTPO in treatment of immune thrombocytopenia%Rituximab单药与联合rhTPO治疗免疫性血小板减少症对照研究

    Institute of Scientific and Technical Information of China (English)

    颜金花; 李萍; 邬国和; 谌萍丽; 陈建兰; 李慧慧; 汤爱萍

    2016-01-01

    目的 研究Rituximab(利妥昔单抗,中文名:美罗华)单药与联合rhTPO(重组人血小板生成素)治疗免疫性血小板减少症(ITP)的效果对照.方法 病例资料来源于我院2015年1~12月确诊ITP患者40例.根据药物治疗方式的差异将40例患者分为LD-RTX单药组20例和LD-RTX联合rhTPO用药组20例.利妥昔单抗(RTX)标准剂量为(375 mg/m2每周,4周),重组人全长糖基化TPO(rhTPO)是血小板生成素受体激动剂,剂量为300 U/(kg·d),每日一次,连续使用14 d;待血小板计数恢复至100x109/L以上,或血小板计数绝对值升高≥50x109/L时即停用.比较两组患者的总有效率、死亡率、患者起效时间、维持时间的差异及安全性.结果 (1)LD-RTX联合rhTPO用药组对比LD-RTX单药组总有效率更高,分别为90.00%和65.00% (P<0.05);(2) LD-RTX联合rhTPO用药组对比LD-RTX单药组死亡率更低,分别为0和15.00% (P<0.05);(3) LD-RTX联合rhTPO用药组对比LD-RTX单药组起效时间更短,维持时间更长,其中,LD-RTX单药组分别为(22.39±2.77)d、(51.39±5.77)d,LD-RTX联合rhTPO用药组分别为(7.51±1.41)d、(79.51±12.41)d,差异有统计学意义(P<0.05).(4)两组均无严重副作用发生.结论 Rituximab单药与联合rhTPO治疗免疫性血小板减少症均有一定效果,与单药比较,采用rhTPo和LD-RTX联合治疗有利于提升疗效和缩短疗程,且药物作用维持时间更长,对于复发患者以及经激素治疗无效的患者来说是一种安全高效的治疗方法.

  18. Late hepatitis B virus reactivation after lamivudine prophylaxis interruption in an anti-HBs-positive and anti-HBc-negative patient treated with rituximab-containing therapy.

    Science.gov (United States)

    Ceccarelli, Laura; Salpini, Romina; Sarmati, Loredana; Svicher, Valentina; Bertoli, Ada; Sordillo, Pasquale; Ricciardi, Alessandra; Perno, Carlo Federico; Andreoni, Massimo; Sarrecchia, Cesare

    2012-08-01

    We describe a case of an anti-HBs-positive patient who experienced hepatitis B reactivation 18 months after the discontinuation of rituximab and after 12 months of lamivudine prophylaxis. The patient carried a hepatitis B genotype D virus harbouring a single immune escape mutation, sT118K. No consensus guidelines regarding the optimal length of treatment or the best elective drug have been defined for antiviral prophylaxis for HBsAg-negative, anti-HBc- and/or anti-HBs-positive patients undergoing immunosuppressive treatment. Screening based on HBV serological markers and HBV DNA testing is a critical issue to recognise hepatitis B reactivation as early as possible. Furthermore, it is of outstanding importance to identify alternative markers (e.g. cccDNA, HBV core related antigen, etc.), that could be predictive of HBV reactivation.

  19. Pulmonary intravascular large B-cell lymphoma successfully treated with rituximab, cyclophosphamide, vincristine, doxorubicin and prednisolone immunochemotherapy: Report of a patient surviving for over 1 year.

    Science.gov (United States)

    Nishii-Ito, Shizuka; Izumi, Hiroki; Touge, Hirokazu; Takeda, Kenichi; Hosoda, Yuzuru; Yamasaki, Akira; Kuwamoto, Satoshi; Shimizu, Eiji; Motokura, Toru

    2016-12-01

    A 73-year-old man with a history of lethargy, fever and dyspnea was admitted to Tottori University Hospital. A computed tomography (CT) scan revealed splenomegaly and diffusely spreading ground-glass opacities (GGOs) in both lungs. A video-assisted thoracoscopic surgery (VATS)-guided lung biopsy revealed intravascular proliferation of large atypical lymphoid cells in the arteries, veins and alveolar walls. The patient was diagnosed with intravascular large B-cell lymphoma (IVLBCL); he received 6 cycles of rituximab, cyclophosphamide, doxorubicin, vincristine and prednisolone (R-CHOP) immunochemotherapy and has remained in complete remission for >1 year. Although IVLBCL is a rare disease, it should be considered in the differential diagnosis of pulmonary diffuse lesions that present with GGOs on CT scans.

  20. Diffuse Large B-Cell Lymphoma Transformed from Mucosa-Associated Lymphoid Tissue Lymphoma Arising in a Female Urethra Treated with Rituximab for the First Time

    Directory of Open Access Journals (Sweden)

    A. Al Zahrani

    2012-05-01

    Full Text Available A 30-year-old female patient presented to the gynecology clinic with a small (painless swelling at the urethral orifice. She underwent surgical excision of the lesion. Pathological examination revealed non-Hodgkin’s lymphoma of diffuse large B-cell type and mucosa-associated lymphoid tissue type, stage IE. The patient refused radiotherapy. Accordingly, we started CHOP-R chemotherapy. She received a total of 6 cycles of CHOP and 8 cycles of rituximab. Patient follow-up was done 3 months later through CT scan and cytoscopy confirming the complete remission. The patient has been disease-free for 4 years. We reviewed 26 cases of this rare entity reported previously.

  1. [Reccurent Clostridium difficile infection in patient after kidney transplantation on rituximab therapy due to PTLD (Post-Transplant Lymphoprolipherative Disorder). First experience with Fidaxomicin use--case report].

    Science.gov (United States)

    Cieniawski, Dominik; Ignacak, Ewa; Bętkowska-Prokop, Alina; Dudzik, Barbara; Walatek, Bogusław; Kuźniewski, Marek; Sułowicz, Władysław

    2014-01-01

    Clostridium difficile infection (CDI) is an increasingly problem in everyday clinical practice. The most important risk factor of this infection is antibiotics use. The incidence of Clostridium difficile associated diarrhea (CDAD) in patients after renal transplantation is estimated to be about 6% in the early postoperative period. Due to the applied immunosuppression and frequent infections requiring intensive, broad spectral antibiotics, the later prevalence of CDAD may remain at a similar level. Massive diarrhea caused by Clostridium difficile may lead to fluctuations in immunosuppressive drugs concentration, in renal transplant patients. The authors present a case study of a 23-year old patient after kidney transplantation from deceased donor, with diagnosed polymorphic PTLD (Post-Transplant Lymphoproliferative Disorder). During biological treatment with rituximab in this patient 4 recurrences of CDI were observed. In this article the clinical manifestation of recurrent CDAD are presented. The authors discuss therapeutic procedure with fidaxomicin use, its results and influence on immunosuppressive drugs concentration.

  2. 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

    2016-10-19

    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.Methods: 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; 1-5. ©2016 AACR.

  3. Long-term remission in mantle cell lymphoma following high-dose sequential chemotherapy and in vivo rituximab-purged stem cell autografting (R-HDS regimen).

    Science.gov (United States)

    Gianni, Alessandro M; Magni, Michele; Martelli, Maurizio; Di Nicola, Massimo; Carlo-Stella, Carmelo; Pilotti, Silvana; Rambaldi, Alessandro; Cortelazzo, Sergio; Patti, Caterina; Parvis, Guido; Benedetti, Fabio; Capria, Saveria; Corradini, Paolo; Tarella, Corrado; Barbui, Tiziano

    2003-07-15

    Mantle cell lymphoma (MCL) is rarely cured with standard-dose chemotherapy. From January 1997 to February 2000, 28 previously untreated advanced-stage MCL patients younger than 61 years of age were treated at 9 Italian hematologic departments with 3 cycles of standard-dose debulking chemotherapy followed by a high-dose rituximab-supplemented sequence (R-HDS) including intravenous administration of high-dose cyclophosphamide, high-dose cytarabine, high-dose melphalan, and high-dose mitoxantrone plus melphalan. Study end points included toxicity, clinical and molecular response rates, long-term event-free survival (EFS), and overall survival (OS) rates, as well as the ability to harvest tumor-free peripheral blood stem cells. Optimal amounts of polymerase chain reaction-negative (PCR-negative) CD34+ cells were collected from all 20 informative patients. One patient died of toxicity. All 27 patients assessable for response achieved a complete response (CR), of which 24 remain in continuous complete remission (CCR) after a median follow-up of 35 months. Three patients had transient evidence of PCR-detectable disease in the bone marrow. The OS and EFS rates at 54 months were 89% and 79%, respectively. These results compare with the 42% OS rate and the 18% EFS rate observed in 35 age-matched historic controls treated with standard-dose chemotherapy at the participating centers. The use of rituximab in combination with high-dose chemotherapy represents a very effective in vivo purging method. The R-HDS regimen can be safely applied in a multicenter hematology setting and leads to long-term EFS and OS in the majority of patients with an otherwise incurable disease.

  4. 131Ⅰ-rituximab therapy of B cell non-Hodgkin lymphoma%131Ⅰ-rituximab治疗B细胞非霍奇金淋巴瘤

    Institute of Scientific and Technical Information of China (English)

    蔡秋琼; 杜明华

    2008-01-01

    放射免疫治疗是将单克隆抗体(单抗)耦联放射性核素,在肿瘤局部产生足够的电离辐射生物学效应,达到高效、低毒的治疗效果.非霍奇金淋巴瘤(NHL)是最常见的淋巴系统恶性肿瘤之一,其绝大多数是B细胞来源,细胞分化抗原CD20是放射免疫治疗B细胞NHL的最佳靶点,用131Ⅰ标记rituximab(一种抗CD20单抗)在治疗B细胞NHL的临床研究中显示出良好的效果,但仍存在许多问题,人们正在进一步研究解决此类问题,以取得更好的治疗效果.%Radioimmunotherapy,a kind of internal radiation therapy,can achieve high performance and low toxicity by fewer monoclonal antibodies couple radioactive nuclides,created sufficient ionization biologic effect on tumor.Non-Hodgkin lymphoma(NHL) is the most common hematological malignancy.Most of them are B cell lymphomas.CD20 is the best target of radioimmunotherapy on B cell-NHL.Clinical trials indicate 131Ⅰ-rituximab is effective on B cell-NHL,while many problems are existed.Approaches are under investigation to improve outcomes in patients with B cell-NHL.

  5. Bendamustine plus rituximab versus R-CHOP as first-line treatment for patients with indolent non-Hodgkin's lymphoma: evidence from a multicenter, retrospective study.

    Science.gov (United States)

    Mondello, Patrizia; Steiner, Normann; Willenbacher, Wolfgang; Wasle, Ines; Zaja, Francesco; Zambello, Renato; Visentin, Andrea; Mauro, Endri; Ferrero, Simone; Ghione, Paola; Pitini, Vincenzo; Cuzzocrea, Salvatore; Mian, Michael

    2016-06-01

    The optimal first-line treatment for advanced low-grade non-Hodgkin lymphomas (LG-NHL) is still highly debated. Recently, the StiL and the BRIGHT trials showed that the combination of rituximab and bendamustine (R-B) is non-inferior to rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) with a better toxicity profile. Utilizing a retrospective analysis, we compared the efficacy and safety of both regimens in clinical practice. From November 1995 to January 2014, 263 LG-NHL patients treated with either R-B or R-CHOP were retrospectively assessed in seven European cancer centers. Ninety patients were treated with R-B and 173 with R-CHOP. Overall response rate was 94 and 92 % for the R-B and the R-CHOP group, respectively. The percentage of complete response was similar for both groups (63 vs. 66 % with R-B and R-CHOP, respectively; p = 0.8). R-B was better tolerated and less toxic than R-CHOP. The median follow-up was 6.8 and 5.9 years for the R-CHOP and the R-B group, respectively. Overall, no difference in progression-free survival (PFS) (108 vs. 110 months; p = 0.1) was observed in the R-B group compared to the R-CHOP cohort. Nevertheless, R-B significantly prolonged PFS in FL patients (152 and 132 months in the R-B and R-CHOP group, respectively; p = 0.05). However, this result was not verified in multivariate analysis probably due to the limits of the present study. We confirm that the R-B regimen administered in patients with LG-NHL is an effective and less toxic therapeutic option than R-CHOP in clinical practice.

  6. CURRENT APPROACH TO DEVELOPMENT OF BIOSIMILAR PRODUCTS CONTAINING MONOCLONAL ANTIBODIES AS AN ACTIVE SUBSTANCE – NON-CLINICAL AND CLINICAL STUDIES OF THE FIRST RUSSIAN RITUXIMAB BIOSIMILAR, ACELLBIA®

    Directory of Open Access Journals (Sweden)

    S. M. Alekseev

    2015-01-01

    Full Text Available Objective. Evaluation of pharmacokinetics, pharmacodynamics, safety and efficacy of rituximab biosimilar (Acellbia,  BIOCAD, Russia used as  monotherapy in patients with indolent B-cell non-Hodgkin’s lymphoma in comparison with the parameters of innovator rituximab – MabThera.Materials and methods. 92 patients (aged 18 years and older with diagnosed CD20-positive follicular non-Hodgkin’s lymphoma, stage II-IV by Ann Arbor, 1-2 histologic grade, or marginal zone lymphoma were enrolled into the study. Patients were randomised in 1:1 ratio to receive 375 mg/sq.m of Acellbia or MabThera on days 1, 8, 15 and 22.Results. Overall response rate in both arms was equivalent: 39.52% in BCD-020 arm and 36.57% of patients in RTX arm (p=0.8250. Within the first week after a single infusion of Acellbia or MabThera, the level of  CD19 and CD20-positive cells rapidly decreased to almost undetectable values without any obvious recovery by the end of observation (upon intergroup comparison p>0.05 at all specified time points. 90% CI for the geometric mean of a Acellbia/MabThera  AUC0-t ratio fell within standard bioequivalence range 80-125% (80.1-118.2% for the ratio of AUC0-168 after a single dose. Within the whole study period  the frequency of AEs, including severe AEs (grade 3-4, associated with the use of monotherapy, were equal in both arms without any significant differences. Conclusions. Acellbia is non-inferior to MabThera in terms of efficacy, pharmacokinetics, pharmacodynamics and immunogenicity. Acellbia was well tolerated, with the safety profile comparable with MabThera’s parameters.

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

    Directory of Open Access Journals (Sweden)

    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

  8. Molecular Monitoring after Autologous Stem Cell Transplantation and Preemptive Rituximab Treatment of Molecular Relapse; Results from the Nordic Mantle Cell Lymphoma Studies (MCL2 and MCL3) with Median Follow-Up of 8.5 Years

    DEFF Research Database (Denmark)

    Kolstad, Arne; Pedersen, Lone Bredo; Eskelund, Christian W

    2017-01-01

    -risk Mantle Cell Lymphoma International Prognostic Index score and positive MRD status pre-ASCT predicted early molecular relapse. In conclusion, preemptive rituximab treatment converts patients to MRD negativity and likely postpones clinical relapse. Molecular monitoring offers an opportunity to select some......The main objectives of the present study were to monitor minimal residual disease (MRD) in the bone marrow of patients with mantle cell lymphoma (MCL) to predict clinical relapse and guide preemptive treatment with rituximab. Among the patients enrolled in 2 prospective trials by the Nordic...... Lymphoma Group, 183 who had completed autologous stem cell transplantation (ASCT) and in whom an MRD marker had been obtained were included in the our analysis. Fresh samples of bone marrow were analyzed for MRD by a combined standard nested and quantitative real-time PCR assay for Bcl-1/immunoglobulin...

  9. Primary therapy of Waldenstrom macroglobulinemia (WM) with weekly bortezomib, low-dose dexamethasone, and rituximab (BDR): long-term results of a phase 2 study of the European Myeloma Network (EMN).

    Science.gov (United States)

    Dimopoulos, Meletios A; García-Sanz, Ramón; Gavriatopoulou, Maria; Morel, Pierre; Kyrtsonis, Marie-Christine; Michalis, Eurydiki; Kartasis, Zafiris; Leleu, Xavier; Palladini, Giovanni; Tedeschi, Alessandra; Gika, Dimitra; Merlini, Giampaolo; Kastritis, Efstathios; Sonneveld, Pieter

    2013-11-07

    In this phase 2 multicenter trial, we evaluated the activity of bortezomib, dexamethasone, and rituximab (BDR) combination in previously untreated symptomatic patients with Waldenström macroglobulinemia (WM). To prevent immunoglobulin M (IgM) "flare," single agent bortezomib (1.3 mg/m(2) IV days 1, 4, 8, and 11; 21-day cycle), was followed by weekly IV bortezomib (1.6 mg/m(2) days 1, 8, 15, and 22) every 35 days for 4 additional cycles, followed by IV dexamethasone (40 mg) and IV rituximab (375 mg/m(2)) in cycles 2 and 5. Fifty-nine patients were treated; 45.5% and 40% were high and intermediate risk per the International Prognostic Scoring System for WM. On intent to treat, 85% responded (3% complete response, 7% very good partial response, 58% partial response [PR]). In 11% of patients, an increase of IgM ≥25% was observed after rituximab; no patient required plasmapheresis. After a minimum follow-up of 32 months, median progression-free survival was 42 months, 3-year duration of response for patients with ≥PR was 70%, and 3-year survival was 81%. Peripheral neuropathy occurred in 46% (grade ≥3 in 7%); only 8% discontinued bortezomib due to neuropathy. BDR is rapidly acting, well tolerated, and nonmyelotoxic, inducing durable responses in previously untreated WM.

  10. 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

  11. Rapid-progressive decrease of cognitive and physical functions due to rituximab%利妥昔单抗致认知和躯体功能障碍

    Institute of Scientific and Technical Information of China (English)

    李进峰; 闫秀娟; 张金彪; 张媛

    2015-01-01

    A 63-year-old female with non-Hodgkin′s lymphoma was treated with a chemotherapeutic regimen composed of rituximab,cyclophosphamide,doxorubicin,vincristine,prednisolone( R-CHOP). She was given rituximab 600 mg plus 750 ml of 0. 9% sodium chloride injection intravenous drip on the first day, at the same time treatments for hydration,alkalization,protecting visceral function,prevention of adverse reactions were given. On day 2,the patient developed an involuntary shaking limbs,a lower limbs weakness,a slightly slow reaction and an unsteady gait. MRI of the brain did not show any significant finding. On day 3,she had a fever,cognitive impairment and confusion. On day 4,the patient could not have independent feeding and defecation. Methyl prednisolone,drugs for improving microcirculation and rehydration therapy were applied. Two days later, the patient′s consciousness restored. He can eat independently,defecate by himself,and his limbs and neuropsychological symptoms were relieved. Five days later,the symptoms were apparently improved.%1例63岁女性患者因非霍奇金淋巴瘤拟行R-CHOP(利妥昔单抗、环磷酰胺、阿霉素、长春新碱、泼尼松龙)方案治疗。首日给予利妥昔单抗600 mg加入0.9%氯化钠注射液750 ml静脉滴注,同时给予水化、碱化、保护脏器功能、预防不良反应等治疗。第2天患者出现四肢不自主抖动、双下肢乏力、反应略迟钝和行走不稳,头颅磁共振成像检查未见异常;第3天出现发热、认知障碍;第4天不能自主进食及自主排便。给予甲泼尼龙琥珀酸钠、改善微循环、补液等支持治疗,2d后患者意识转清,可自主进食、排便,四肢和神经精神症状缓解,5d后症状明显减轻。

  12. Value of Surveillance Studies for Patients With Stage I to II Diffuse Large B-Cell Lymphoma in the Rituximab Era

    Energy Technology Data Exchange (ETDEWEB)

    Hiniker, Susan M.; Pollom, Erqi L. [Department of Radiation Oncology, Stanford Cancer Institute, Stanford, California (United States); Khodadoust, Michael S. [Division of Oncology, Department of Medicine, Stanford Cancer Institute, Stanford, California (United States); Kozak, Margaret M. [Department of Radiation Oncology, Stanford Cancer Institute, Stanford, California (United States); Xu, Guofan; Quon, Andrew [Division of Nuclear Medicine, Department of Radiology, Stanford Cancer Institute, Stanford, California (United States); Advani, Ranjana H. [Division of Oncology, Department of Medicine, Stanford Cancer Institute, Stanford, California (United States); Hoppe, Richard T., E-mail: rhoppe@stanford.edu [Department of Radiation Oncology, Stanford Cancer Institute, Stanford, California (United States)

    2015-05-01

    Background: The role of surveillance studies in limited-stage diffuse large B-cell lymphoma (DLBCL) in the rituximab era has not been well defined. We sought to evaluate the use of imaging (computed tomography [CT] and positron emission tomography [PET]-CT) scans and lactate dehydrogenase (LDH) in surveillance of patients with stage I to II DLBCL. Methods: A retrospective analysis was performed of patients who received definitive treatment between 2000 and 2013. Results: One hundred sixty-two consecutive patients with stage I to II DLBCL were treated with chemotherapy +/− rituximab, radiation, or combined modality therapy. The 5-year rates of overall survival (OS) and freedom from progression (FFP) were 81.2% and 80.8%, respectively. Of the 162 patients, 124 (77%) were followed up with at least 1 surveillance PET scan beyond end-of-treatment scans; of those, 94 of 124 (76%) achieved a complete metabolic response on PET scan after completion of chemotherapy, and this was associated with superior FFP (P=.01, HR=0.3) and OS (P=.01, HR 0.3). Eighteen patients experienced relapse after initial response to therapy. Nine relapses were initially suspected by surveillance imaging studies (8 PET, 1 CT), and 9 were suspected clinically (5 by patient-reported symptoms and 4 by symptoms and physical examination). No relapses were detected by surveillance LDH. The median duration from initiation of treatment to relapse was 14.3 months among patients with relapses suspected by imaging, and 59.8 months among patients with relapses suspected clinically (P=.077). There was no significant difference in OS from date of first therapy or OS after relapse between patients whose relapse was suspected by imaging versus clinically. Thirteen of 18 patients underwent successful salvage therapy after relapse. Conclusions: A complete response on PET scan immediately after initial chemotherapy is associated with superior FFP and OS in stage I to II DLBCL. The use of PET scans as

  13. ILY重组蛋白增强利妥昔单抗杀伤骨髓瘤ARH-77细胞的实验研究%Application of ILY recombinant protein in Rituximab to treat myeloma cells

    Institute of Scientific and Technical Information of China (English)

    尤涛; 徐勇; 余玲

    2011-01-01

    Objective Through observing the CDC effect of CD59 inhibitor ILY recombinant protein in Rituximab to treat multiple myeloma ( MM ) ARH-77 cells, we investigate the feasibility of combination with ILY recombinant protein in MM therapy. Methods The expression of CD20 and CD59 in ARH-77 cells was analyzed by FACS. Cells death percentages were measured by alarma blue and typan blue in ARH-77 cells treated with ILY recombinant protein and Rituximab. Results High levels of CD20 and CD59 were detected on the surface of ARH-77 cells. ILY recombinant protein effectively enhanced CDC effect and reversed drug resistance mediated by Rituximab in MM cells. Conclusion The ILY recombinant protein significantly improves Rituximab effect in MM cells therapy,and may be a good adjunctive drug in monoclonal antibodies treatment with tumors.%目的 通过体外实验观察CD59抑制物ILY重组蛋白增强利妥昔单抗(Rituximab)对多发性骨髓瘤ARH-77细胞的补体依赖性细胞毒性效应(CDC效应),探讨联合应用该蛋白治疗多发性骨髓瘤的可行性.方法 FACS分析法侦测ARH-77细胞系的CD20和CD59抗原表达.Alarma blue及Typan blue法观察联合应用ILY重组蛋白及利妥昔单抗对骨髓瘤ARH-77细胞的CDC效应.结果 ARH-77细胞呈现高的CD20及CD59抗原表达;联合应用ILY重组蛋白,能增强利妥昔单抗对ARH-77细胞的CDC效应,逆转其耐药性.结论 ILY重组蛋白可有效地增强利妥昔单抗对多发性骨髓瘤细胞的杀伤效应,有望成为一种新的单克隆抗体治疗肿瘤的辅助药物.

  14. Uso do rituximabe para o tratamento da plaquetopenia do lúpus eritematoso sistêmico: eficácia clínica e efeito nas moléculas de co-estimulação Use of rituximab for the treatment of systemic lupus erythematosus' thrombocytopenia: clinical efficacy and costimulatory molecules effect

    Directory of Open Access Journals (Sweden)

    Mittermayer B. Santiago

    2006-04-01

    Full Text Available Plaquetopenia é uma complicação não raramente vista no contexto do lúpus eritematoso sistêmico (LES. O seu tratamento inclui o uso de corticosteróide, imunossupressores, imunoglobulina humana e, eventualmente, esplenectomia. Descreve-se um caso de LES com plaquetopenia persistente a despeito do uso de prednisona e azatioprina, que respondeu satisfatoriamente ao uso de rituximabe (RTX. O estudo de citometria de fluxo mostrou depleção dos linfócitos B do sangue periférico, assim como uma queda das moléculas de co-estimulação após o uso da medicação. Não foi observado efeito colateral relacionado à infusão da substância. Dessa forma, o RTX parece estar indicado para casos selecionados de LES com plaquetopenia de difícil controle.Thrombocytopenia is not a rare complication in patients with systemic lupus erythematosus (SLE. Its treatment includes the use of corticosteroids, immunosuppressive drugs, intravenous immunoglobulin and, eventually, splenectomy. We describe a SLE patient with persistent thrombocytopenia despite of the use of prednisone and azathioprine that improved after infusion of rituximab (RTX. Flow cytometry analysis revealed depletion of B cells from the peripheral blood as well as a decrease in costimulatory molecules after the administration of the medication. Side effects related to the infusion were not observed. It suggests that RTX may be indicated in selected cases of SLE with thrombocytopenia of difficult control.

  15. Safety and efficacy of rituximab plus bendamustine in relapsed or refractory diffuse large B-cell lymphoma patients: an Italian retrospective multicenter study.

    Science.gov (United States)

    Arcari, Annalisa; Chiappella, Annalisa; Spina, Michele; Zanlari, Luca; Bernuzzi, Patrizia; Valenti, Vanessa; Tani, Monica; Marasca, Roberto; Cabras, Maria Giuseppina; Zambello, Renato; Santagostino, Alberto; Ilariucci, Fiorella; Carli, Giuseppe; Musto, Pellegrino; Savini, Paolo; Marino, Dario; Ghio, Francesco; Gentile, Massimo; Cox, Maria Christina; Vallisa, Daniele

    2016-08-01

    Relapsed or refractory diffuse large B-cell lymphoma (DLBCL) not suitable for high dose chemotherapy with autologous stem cell transplantation (ASCT) has a dismal prognosis and no standard therapy. We designed an Italian multicenter retrospective study aimed at evaluating the safety and efficacy of rituximab plus bendamustine (R-B) as salvage treatment in patients not eligible for ASCT because of age and/or comorbidity or in patients with post-ASCT recurrence. Fifty-five patients with a median age of 76 years were included. The overall response rate was 50%, including 28% complete remission and 22% partial remission. The median overall survival (OS) was 10.8 months. The median progression free survival (PFS) was 8.8 months. Eleven patients are still alive and in complete remission at last follow-up (12-71 months). Toxicity was moderate, mainly grades 1 and 2. R-B showed promising efficacy results with an acceptable toxicity profile and should be further investigated, possibly in combination with novel drugs.

  16. A Case of Subacute Cutaneous Lupus Erythematosus in a Patient with Mixed Connective Tissue Disease: Successful Treatment with Plasmapheresis and Rituximab

    Directory of Open Access Journals (Sweden)

    M. Fantò

    2013-01-01

    Full Text Available A 30-year-old woman affected by Mixed Connective Tissue Disease with scleroderma spectrum developed a facial eruption, a clinical and histological characteristic of subacute cutaneous lupus erythematosus (SCLE. Speckled anti-nuclear antibodies, high-titer anti-ribonucleoprotein1, anti-Sm, anti-Cardiolipin (aCL IgG/IgM, and anti-Ro/SSA antibodies were positive. SCLE was resistant to Azathioprine, Hydroxychloroquine, and Methotrexate while Mycophenolate Mofetil was suspended due to side effects. Subsequently, the patient was treated with three cycles of therapeutic plasma exchange (TPE followed, one month after the last TPE, by the anti-CD20 antibody Rituximab (RTX (375 mg/m2 weekly for 4 weeks. Eight and 16 months later the patient received other two TPE and RTX cycles, respectively. This therapeutic approach has allowed to obtain a complete skin healing persistent even after 8-month follow-up. Moreover, mitigation of Raynaud's phenomenon, resolution of alopecia, and a decline of aCL IgG/IgM and anti-Ro/SSA antibodies were observed.

  17. Addition of lenalidomide to rituximab, ifosfamide, carboplatin, etoposide (RICER) in first-relapse/primary refractory diffuse large B-cell lymphoma.

    Science.gov (United States)

    Feldman, Tatyana; Mato, Anthony R; Chow, Kar F; Protomastro, Ewelina A; Yannotti, Kara M L; Bhattacharyya, Pritish; Yang, Xiao; Donato, Michele L; Rowley, Scott D; Carini, Carolanne; Valentinetti, Marisa; Smith, Judith; Gadaleta, Gabriella; Bejot, Coleen; Stives, Susan; Timberg, Mary; Kdiry, Sabrina; Pecora, Andrew L; Beaven, Anne W; Goy, Andre

    2014-07-01

    Relapsed/refractory diffuse large B-cell lymphoma (DLBCL) is associated with a poor prognosis. Outcomes are particularly poor following immunochemotherapy failure or relapse within 12 months of induction. We conducted a Phase I/II trial of lenalidomide plus RICE (rituximab, ifosfamide, carboplatin, and etoposide) (RICER) as a salvage regimen for first-relapse or primary refractory DLBCL. Dose-escalated lenalidomide was combined with RICE every 14 d. After three cycles of RICER, patients with chemosensitive disease underwent stem cell collection and consolidation with BEAM [BCNU (carmustine), etoposide, cytarabine, melphalan] followed by autologous stem cell transplantation (autoSCT). Patients who recovered from autoSCT toxicities within 90 d initiated maintenance treatment with lenalidomide 25 mg daily for 21 d every 28 d for 12 months. No dose-limiting or unexpected toxicities occurred with lenalidomide 25 mg plus RICE. Grade 3/4 haematological toxicities resolved appropriately, and planned dose density and dose intensity of RICER were preserved. No lenalidomide or RICE dose reductions were required in any of the three cycles. After two cycles of RICER, nine of 15 patients (60%) achieved a complete response, and two achieved a partial response (13%). Combining lenalidomide with RICE is feasible, and results in promising response rates (particularly complete response rates) in high-risk DLBCL patients.

  18. Bendamustine + rituximab chemoimmunotherapy and maintenance lenalidomide in relapsed, refractory chronic lymphocytic leukaemia and small lymphocytic lymphoma: A Wisconsin Oncology Network Study.

    Science.gov (United States)

    Chang, Julie E; Havighurst, Thomas; Kim, KyungMann; Eickhoff, Jens; Traynor, Anne M; Kirby-Slimp, Rachel; Volk, Lynn M; Werndli, Jae; Go, Ronald S; Weiss, Matthias; Blank, Jules; Kahl, Brad S

    2016-04-01

    Bendamustine + rituximab (BR) has demonstrated high response rates in relapsed/refractory (R/R) chronic lymphocytic leukaemia (CLL) and small lymphocytic lymphoma (SLL). However, progression-free survival (PFS) after BR is lenalidomide after BR induction could improve PFS in R/R CLL/SLL. Thirty-four patients with R/R CLL/SLL who had received 1-5 prior chemotherapy regimens were treated with 6 cycles of BR induction. Patients achieving at least a minor response received twelve 28-d cycles of lenalidomide 5-10 mg/d. The primary endpoint was PFS. The median age was 67 years, with a median of 2 prior therapies. Eleven patients had confirmed presence of 17p and/or 11q deletions. Twenty-five (74%) completed 6 cycles of induction BR (response rate 56%). Nineteen (56%) patients received maintenance lenalidomide; only 6 patients completed the intended 12 cycles, highlighting the limited feasibility of lenalidomide in this setting, primarily due to haematological and infectious toxicities. The observed median PFS of 18·3 months is not significantly different from that of BR induction in R/R CLL/SLL without maintenance therapy (15·2 months). It is possible that lenalidomide maintenance may be more feasible and effective in the front-line setting, which is being tested in an ongoing trial (NCT01754857).

  19. 177Lu标记单克隆抗体Rituximab及其初步生物学评价%Preparation and Preliminary Biological Evaluation of 177Lu Labelled Rituximab

    Institute of Scientific and Technical Information of China (English)

    马秀凤; 张君丽; 李洪玉; 梁积新; 杨云; 杨春慧; 杜进

    2014-01-01

    以CHX-A'-DTPA和p-SCN-Bz-DTPA为双功能螯合剂,分别对Rituximab进行偶联,用177Lu进行标记,制备177 Lu-Rituximab.在优化条件下,177 Lu对单抗偶联物CHX-A"-DTPA-Rit uximab和p-SCN-Bz-DT-PA-Rituximab的标记率和放化纯度均大于99%.室温及37℃条件下,177Lu-Rituximab在各种测试体系中均显示良好的体外稳定性.在正常小鼠体内的生物分布结果显示,177Lu-Rituximab发生了分解,游离的177Lu在骨中形成较高浓集.177Lu-p-SCN-Bz-DTPA-Rituximab比177Lu-CHX-A"-DTPA-Rituximab的体内清除快,而且游离177 Lu的骨摄取低,结果表明,p-SCN-Bz-DTPA更适于作为双功能螯合剂用于单抗的177Lu标记.

  20. Agranulocytosis under biotherapy in rheumatoid arthritis: three cases hypothesis of parvovirus B19 involvement in agranulocytosis observed under tocilizumab and rituximab for the treatment of rheumatoid arthritis.

    Science.gov (United States)

    Giraud, C; Tatar, Z; Soubrier, M

    2016-10-01

    Leukopenia is a considerably common complication of tocilizumab [TCZ] and rituximab [RTX] therapy. RTX-induced leukopenia typically exhibits delayed onset. While agranulocytosis has been reported linked to RTX treatment of lymphoma, this complication rarely occurs in rheumatoid arthritis (RA) treatment and, to our knowledge, has never been reported in association with TCZ therapy. We herein report four agranulocytosis cases in three patients, with the first two cases suspected to be secondary to human parvovirus B19 (PVB19) infection. Agranulocytosis manifested in the first patient 2 months following a third RTX course. Bone marrow (BM) polymerase chain reaction (PCR) was positive for PVB19. The patient relapsed after three TCZ courses, with her PCR again positive for PVB19. Both episodes resolved under granulocyte-macrophage colony-stimulating factor (GM-CSF). In the second patient, agranulocytosis manifested after the 74th TCZ course. Bone marrow PCR was positive for PVB19, and the evolution was favorable under intravenous immunoglobulin administration. The third case was a 53-year-old female patient with seropositive RA who presented agranulocytosis after the first infusion of her fourth RTX course. Unfortunately, no PCR PVB19 was made on myelogram. Evolution was favorable after 5 days of GM-CSF. PVB19 infection should be investigated in patients suffering from agranulocytosis manifesting during biotherapy. In cases manifesting from the 15th day of RTX treatment onwards, hemogram must be conducted before readministering the infusion.

  1. RUSSIAN EXPERIENCE WITH USING MONOCLONAL ANTIBODIES TO B-LYMPHOCYTES (RITUXIMAB IN SYSTEMIC VASCULITIDES ASSOCIATED WITH NEUTROPHIL CYTOPLASMIC ANTIBODIES (PRELIMINARY RESULTS OF THE RUSSIAN REGISTER NORMA

    Directory of Open Access Journals (Sweden)

    T. V. Beketova

    2014-01-01

    Full Text Available In 2013, Russia registered officially the indications for the use of monoclonal antibodies to B-lymphocytes (rituximab, RTM in systemic vasculitides associated with antineutrophil cytoplasmic antibodies (ANCA-SV. This communication presents the preliminary results of the Russian register of the RTM application in autoimmune diseases (NORMA that has included 50 patients with ANCA-SV treated in 14 cities of the Russian Federation. Twenty-five of 50 (50% patients received repeated courses of RTM. RTM has demonstrated a high efficacy and a good profile of treatment safety in patients with ANCA-SV in real-life national clinical practice. Among 25 patients who had been followed up for over 12 months, the remission was achieved in 92% of cases, a decrease in the ANCA-SV activity was observed in 8%. The efficacy of RTM increased when performing repeated courses, while it has been noted that the positive results can be obtained by prescribing a repeated course of RTM at a reduced dose (500–1000 mg. Prescription of the repeated courses was primarily required in patients with granulomatosis and polyangiitis affecting the lungs. Care should be taken when combining RTM treatment with cytostatics (primarily with cyclophosphamide because of the risk of secondary immunodeficiency and infectious adverse events (AE, which have been the most frequent serious AE (12% in patients with ANCA-SV.

  2. Patterns of neutropenia and risk factors for febrile neutropenia of diffuse large B-cell lymphoma patients treated with rituximab-CHOP.

    Science.gov (United States)

    Choi, Yong Won; Jeong, Seong Hyun; Ahn, Mi Sun; Lee, Hyun Woo; Kang, Seok Yun; Choi, Jin-Hyuk; Jin, U Ram; Park, Joon Seong

    2014-11-01

    Febrile neutropenia (FN) is the major toxicity of rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) regimen in the treatment of diffuse large B-cell lymphoma (DLBCL). The prediction of neutropenia and FN is mandatory to continue the planned R-CHOP therapy resulting in successful anti-cancer treatment. The clinical features and patterns of neutropenia and FN from 181 DLBCL patients treated with R-CHOP were analyzed retrospectively. Sixty percent (60.2%) of patients experienced at least one episode of grade 4 neutropenia. Among them, 42.2% of episodes progressed to FN. Forty-eight percent (48.8%) of patients with FN was experienced their first FN during the first cycle of R-CHOP. All those patients never experienced FN again during the rest cycles of R-CHOP. Female, higher stage, international prognostic index (IPI), age ≥65 yr, comorbidities, bone marrow involvement, and baseline serum albumin ≤3.5 mg/dL were significant risk factors for FN by univariate analysis. Among these variables, comorbidities (P=0.009), bone marrow involvement (P=0.006), and female gender (P=0.024) were independent risk factors for FN based on multivariate analysis. On observing the patterns of neutropenia and FN, primary prophylaxis of granulocyte colony-stimulating factor (G-CSF) and antibiotics should be considered particularly in female patients, patients with comorbidities, or when there is bone marrow involvement of disease.

  3. 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.

    Science.gov (United States)

    Visco, Carlo; Tzankov, Alexander; Xu-Monette, Zijun Y; Miranda, Roberto N; Tai, Yu Chuan; Li, Yan; Liu, Wei-min; d'Amore, Emanuele S G; Li, Yong; Montes-Moreno, Santiago; Dybkær, Karen; Chiu, April; Orazi, Attilio; Zu, Youli; Bhagat, Govind; Wang, Huan-You; Dunphy, Cherie H; His, Eric D; Zhao, X Frank; Choi, William W L; Zhao, Xiaoying; van Krieken, J Han; Huang, Qin; Ai, Weiyun; O'Neill, Stacey; Ponzoni, Maurilio; Ferreri, Andres J M; Kahl, Brad S; Winter, Jane N; Go, Ronald S; Dirnhofer, Stephan; Piris, Miguel A; Møller, Michael B; Wu, Lin; Medeiros, L Jeffrey; Young, Ken H

    2013-02-01

    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 been questioned in the new therapeutic era. We analyzed Bcl-2 protein expression, and BCL2 and MYC gene abnormalities by interphase fluorescence in situ hybridization in 327 patients with de novo disease treated with rituximab-CHOP. Isolated BCL2 and MYC rearrangements were not predictive of outcome in our patients as a whole, but only in those with the germinal center subtype of lymphoma. The prognostic relevance of isolated MYC rearrangements was weaker than that of BCL2 isolated translocations, but was probably limited by the rarity of the rearrangements. Seven of eight patients with double hit lymphoma had the germinal center subtype with poor outcome. The germinal center subtype patients with isolated BCL2 translocations had significantly worse outcome than the patients without BCL2 rearrangements (P=0.0002), and their outcome was similar to that of patients with the activated B-cell subtype (P=0.30), but not as bad as the outcome of patients with double hit lymphoma (Pgerminal center subtype lymphoma, but multivariate analysis showed that this was dependent on BCL2 translocations. The gene expression profiling of patients with BCL2 rearrangements was unique, showing activation of pathways that were silent in the negative counterpart. BCL2 translocated germinal center subtype patients have worse prognosis after rituximab-CHOP, irrespective of MYC status, but the presence of combined gene breaks significantly overcomes the prognostic relevance of isolated lesions.

  4. A phase II randomized trial comparing standard and low dose rituximab combined with alemtuzumab as initial treatment of progressive chronic lymphocytic leukemia in older patients: a trial of the ECOG-ACRIN cancer research group (E1908).

    Science.gov (United States)

    Zent, Clive S; Victoria Wang, Xin; Ketterling, Rhett P; Hanson, Curtis A; Libby, Edward N; Barrientos, Jacqueline C; Call, Timothy G; Chang, Julie E; Liu, Jane J; Calvo, Alejandro R; Lazarus, Hillard M; Rowe, Jacob M; Luger, Selina M; Litzow, Mark R; Tallman, Martin S

    2016-03-01

    Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL) patients requiring initial therapy are often older and frailer and unsuitable candidates for standard chemoimmunotherapy regimens. Shorter duration combination monoclonal antibody (mAb) therapy using alemtuzumab and rituximab has been shown to be effective and tolerable treatment for CLL. Standard dose anti-CD20 mAb therapy causes loss of CD20 expression by surviving CLL cells, which can be minimized by decreasing the mAb dose. We report a randomized phase II clinical trial enrolling older (≥ 65 years) patients (median age 76 years, n = 31) with treatment naïve progressive CLL. Patients received 8-12 weeks of standard subcutaneous alemtuzumab with either intravenous standard (375 mg/m(2) weekly)(n = 16) or low dose (20 mg/m(2) 3x week)(n = 15) rituximab. This study was closed before full accrual because the manufacturer withdrew alemtuzumab for treatment of CLL. The overall response rate was 90% with an 45% complete response rate, median progression-free survival of 17.9 months and no significant differences in outcome between the low and standard dose rituximab arms. The major toxicities were cytopenia and infection with one treatment fatality caused by progressive multifocal leukoencephalopathy but no other opportunistic infections. Combination mAb therapy was effective and tolerable treatment for older and frailer patients with progressive CLL, achieving a high rate of complete remissions. These data support the role of mAb in therapy for less fit CLL patients and the further study of low dose higher frequency anti-CD20 mAb therapy as a potentially more effective use of anti-CD20 mAb in the treatment of CLL.

  5. Safety of rituximab in the routine treatment of rheumatoid arthritis in Italy in patients refractory to anti-TNFa drugs: results from the observational retrospective-prospective RUBINO study.

    Science.gov (United States)

    Bazzichi, L; Biasi, D; Tinazzi, E; Muratore, M; Pellerito, R; Russo, R; Corsaro Santi, M; De Sandre, P; Epis, O; Granata, M; Kroegler, B; Meschini, C; Versace, F; Astolfi, C

    2014-11-06

    The paper reports the results from the observational retrospective-prospective RUBINO study conducted in Italy to assess the safety of rituximab in the treatment of rheumatoid arthritis (RA) in routine clinical practice. The percentage of patients who manifested at least one grade 3 or 4 adverse event (AE) assessed by the Common Terminology Criteria for Adverse Events version 3.0 (CTCAE v.3) during the observation period (primary objective) was evaluated. The percentage of patients manifesting a severe AE (SAE), clinical response to rituximab treatment, clinical remission according to disease activity score for 28 joints (DAS28) criteria, markers of disease and quality of life were also assessed. Fifty-three Italian rheumatology centers took part in the study. Patients with a diagnosis of RA and inadequate response to anti-tumor necrosis factor b (anti-TNFa) drugs were enrolled. Participating patients had previously received at least one cycle of rituximab, and treatment was still ongoing at the time of recruitment. Out of 205 patients enrolled, 60% manifested no form of AE, 14.2% had at least one grade 3 or 4 AE, and 11.2% patients reported an SAE. The overall percentage of patients manifesting AEs (40%) was lower compared to the DANCER (81% and 85%), REFLEX (85%) and RESET (85% and 69%) studies, but higher than that observed in the CERERRA registry (from 10.2% to 13.9%). This difference may be due to the shorter observation period applied in the CERERRA registry (only 12 months) compared to the RUBINO study (up to 3 years). All parameters of RA activity (erythrocyte sedimentation rate, C-reactive protein, health assessment questionnaire score, DAS28) improved significantly during the study.

  6. Bendamustine and rituximab combination in the management of chronic lymphocytic leukemia-associated autoimmune hemolytic anemia: a multicentric retrospective study of the French CLL intergroup (GCFLLC/MW and GOELAMS).

    Science.gov (United States)

    Quinquenel, Anne; Willekens, Christophe; Dupuis, Jehan; Royer, Bruno; Ysebaert, Loic; De Guibert, S; Michallet, Anne-Sophie; Feugier, Pierre; Guieze, Romain; Levy, Vincent; Delmer, Alain

    2015-03-01

    We report our experience on bendamustine and rituximab (BR) combination in 26 patients with chronic lymphocytic leukemia (CLL) complicated by autoimmune hemolytic anemia (AIHA). At the time of BR initiation, 88% of the patients had already been treated for AIHA and CLL was progressive regardless of AIHA in all patients but one. Overall response rates were 81% for AIHA and 77% for CLL. Median time to next treatment was 28.3 months and 26.2 months for AIHA and CLL, respectively. BR therapy may represent a good and safe therapeutic option in this setting where adequate control of CLL seems important for long-term AIHA response.

  7. Screen of CD20 mimotope using monoclonal antibody Rituximab%CD20抗原模拟表位的筛选

    Institute of Scientific and Technical Information of China (English)

    吴守振; 张阔; 李萌; 贺丽清; 秦鑫; 张英起

    2009-01-01

    目的:筛选CD20分子的模拟表位肽,构建针对CD20分子的治疗性疫苗,以期为淋巴瘤以及其它B细胞相关性疾病的治疗提供新的方向.方法:利用噬菌体随机呈现肽库筛选技术,以人淋巴细胞分化抗原CD20 mAb Rituximab为靶点,筛选CD20分子的模拟表位肽.通过ELISA方法检测筛选出的阳性噬菌体与Rituximab的特异性结合,并以竞争性结合实验检测筛选出的阳性噬菌体与Raji细胞表面的CD20分子竞争结合Rituximab的能力.最后以Sanger双脱氧链终止法测定DNA序列,推断其氨基酸序列.结果:成功筛选出针对CD20 mAb Rituximab的阳性噬菌体,获得了CD20分子的模拟表位肽QDKLTQWPKWLE.获得的阳性噬菌体能够与Rituximab特异性结合,并且表达该表位的噬菌体可以竞争性抑制Rituximab与天然CD20分子的结合.结论:CD20分子的抗原表位肽QDKLTQWPKWLE能够与mAb Rituximab特异性结合,与天然CD20分子竞争性结合mAb Rituximab,并具有潜在的应用价值.

  8. RITUXIMAB TREATMENT EFFICACY IN PATIENTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS REFRACTORY TO STANDARD THERAPY IN THE LONG-TERM FOLLOW-UP

    Directory of Open Access Journals (Sweden)

    M. E. Tsanyan

    2014-01-01

    Full Text Available Objective. To evaluate the efficacy and safety of rituximab (RTM treatment in the long-term follow-up of patients with systemic lupus erythematosus (SLE refractory to standard therapy. Material and methods. RTM therapy was prescribed to 97 SLE patients with high disease activity and insufficient effica- cy of using high doses of glucocorticoids (GC and cytostatics. The median follow-up time (25th; 75th percentiles was 18 [12; 36] months. The most common clinical manifestations of SLE included nephritis (62%, skin lesion (33%, and lesion of the nervous system (22.7%. The clinical assessment of the SLE activity was carried out using the SLEDAI-2K activity index. In assessing the therapy efficacy, the following concepts were used: the partial response (PR, complete response (CR, and flare. Flare was classified as moderate (MF and severe (SF using the SLE flare index (SFI. Results. Immediately after RTM therapy, depletion of B-cells was determined in 78% of the patients with SLE. During the 6-year follow-up, the effect of RTM therapy was achieved in 84% of the patients after repeated courses of RTM (CR – 56%, PR – 28%. In total, flares were observed in 24 (24.7% patients; the median interval from RTM administration to flare was 12 [12; 24] months. In the long-term follow-up, the decline in the SLEDAI-2K index, normalization of laboratory test values, and the decrease in the daily GC dose were noted. Most patients tolerated well both the first and repeated courses of RTM therapy. Conclusion. According to the results of the long-term follow-up, RTM therapy is a highly effective method to treat SLE patients with the ineffectiveness of previously conducted standard therapy with GC and cytostatics. Good tolerance of RTM treatment has been noted; no increase in risk of infectious complications or adverse reactions has been found. 

  9. The Effect of Combination Therapy with Rituximab and Intravenous Immunoglobulin on the Progression of Chronic Antibody Mediated Rejection in Renal Transplant Recipients

    Directory of Open Access Journals (Sweden)

    Gun Hee An

    2014-01-01

    Full Text Available The treatment for chronic active antibody-mediated rejection (CAMR remains controversial. We investigated the efficacy of rituximab (RTX and intravenous immunoglobulin (IVIg for CAMR. Eighteen patients with CAMR were treated with RTX (375 mg/m2 and IVIg (0.4 g/kg for 4 days. The efficacy of RTX/IVIg combination therapy (RIT was assessed by decline in estimated glomerular filtration rate per month (ΔeGFR before and after RIT. Patients were divided into responder and nonresponder groups based on decrease and no decrease in ΔeGFR, respectively, and their clinical and histological characteristics were compared. Response rate to RIT was 66.7% (12/18, and overall ΔeGFR decreased significantly to 0.4± 1.7 mL·min−1·1.73 m−2 per month 6 months after RIT compared to that observed 6 months before RIT (1.8±1.0, P<0.05. Clinical and histological features between the 12 responders and the 6 nonresponders were not significantly different, but nonresponders had a significantly higher proteinuria levels at the time of RIT (2.5±2.5 versus 7.0±3.5 protein/creatinine (g/g, P<0.001. The effect of the RIT on ΔeGFR had dissipated in all patients by 1 year post-RIT. Thus, RIT delayed CAMR progression, and baseline proteinuria level was a prognostic factor for response to RIT.

  10. Cluster-based comparison of the peptide mass fingerprint obtained by MALDI-TOF mass spectrometry. A case study: long-term stability of rituximab.

    Science.gov (United States)

    Villacorta, Pablo J; Salmerón-García, Antonio; Pelta, David A; Cabeza, José; Lario, Antonio; Navas, Natalia

    2015-03-07

    We evaluated the use of the peptide mass fingerprint (PMF) obtained by matrix assisted laser desorption and ionization (MALDI) time-of-flight mass spectrometry (TOF-MS) to track changes in the structure of a protein. The first problem we had to overcome was the inherent complexity of the PMF, which makes it difficult to compare. We dealt with this problem by developing a cluster-based comparison algorithm which takes into account the proportional error made by the mass spectrometer. This procedure involves grouping together similar masses in an intelligent manner, so that we can determine which data correspond to the same peptide (any slight differences can be explained as experimental errors), and which of them are too different and thus more likely to represent different peptides. The proposed algorithm was applied to track changes in a commercially available monoclonal antibody (mAb), namely rituximab (RTX), prepared under the usual hospital conditions and stored refrigerated (4 °C) and frozen (-20 °C) for a long term study. PMFs were obtained periodically over three months. For each checked time, five replicates of the PMFs were obtained in order to evaluate the similarities between them by means of the occurrences of the particular peptides (m/z). After applying the algorithm to the PMF, different approaches were used to analyse the results. Surprisingly, all of them suggested that there were no differences between the two storage conditions tested, i.e. the RTX samples were almost equally well preserved when stored refrigerated at 4 °C or frozen at -20 °C. The cluster-based methodology is new in protein mass spectrometry and could be useful as an easy test for major changes in proteins and biopharmaceutics for diverse applications in industry and other fields, and could provide additional stability data in relation to the practical use of anticancer drugs.

  11. Treatment of a case of pemphigus vulgaris with combined rituximab%联合rituximab治疗一例寻常型天疱疮的疗效观察

    Institute of Scientific and Technical Information of China (English)

    朱海琴; 潘萌; 李金枝; 周芸; 夏群力; 王颖; 郑捷

    2009-01-01

    Objective To study the efficacy of rituximab in the treatment of pemphigus vulgaris (PV) and its underlying mechanism. Methods A 38-year-old female with PV presented with refractory, painful oral ulcers and erosions. Since she was poorly responsive to prednisone 80 mg daily, intravenous ritu-ximab of 500 mg once a week was given for successive 3 weeks followed by 5 successive days of intra-venous gamma globulin at a dose of 400 mg/kg per day, and a total of two treatment sessions were conducted. ELISA was used to detect the serum titer of anti-Dsg3 antibodies and their IgG subtypes (IgG1 and IgG4) as well as serum level of interferon-gamma (IFN-gamma), interleukin-4 (IL-4), interleukin-10 (IL-10). Results Three months after the end of two treatment sessions, the symptom was obviously improved, and lesions subsided; alter another 1 month, clinical symptom fully disappeared. During the 1-year follow-up, no lesions recurred. The anti-Dsg3 antibody titer was 253.33 U/mL before treatment, plateaued at 250 U/mL within 4 weeks after the initial infusion, decreased till 3 months after the withdrawal, and reached 26.06 U/mL 7 months after the withdrawal, and remained within normal range till the time of this writing. The serum titer of IgGl subclass of anti-Dsg3 antibodies dropped dramatically fight after the first infusion, but that of IgG4 subclass remained at a high level at early stage of medication, began to decline until 3 months after the with-drawal, and finally reached the normal range following clinical remission. Also, serum level of IFN-garnma and IL-10 correlated with the severity of PV. Conclusions Combined rituximab is effective for the control of PV, likely by eliminating Dsg3-specific antibodies, especially IgG4 subclass of them.%目的 观察联合抗CD20单克隆抗体rituximab治疗寻常型天疱疮的临床疗效,探讨其作用机制.方法 寻常型天疱疮患者1例,口腔黏膜顽固性痛性糜烂和溃疡,甲泼尼龙80 mg/d,

  12. Prognostic value of interim (18)F-FDG-PET in diffuse large B cell lymphoma treated with rituximab-based immune-chemotherapy: a systematic review and meta-analysis.

    Science.gov (United States)

    Zhu, Danxia; Xu, Xiao-Li; Fang, Cheng; Ji, Mei; Wu, Jun; Wu, Chang-Ping; Jiang, Jing-Ting

    2015-01-01

    The prognostic value of an interim fluorine-18-fluorodeoxyglucose positron emission tomography ((18)F-FDG PET) for diffuse large B-cell lymphoma (DLBCL) has been assessed by different groups. However, studies have suggested that the use of rituximab could limit the predictive value of interim (18)F-FDG PET for DLBCL. To clarify the prognostic value of interim (18)F-FDG PET in DLBCL patients treated with rituximab based immunochemotherapy, we searched for relevant studies in PubMed, the Cochrane Library and EMBASE. A random versus fixed effects model was applied according to the heterogeneity. According to the literature search strategies, 11 studies were identified. The pooled HR comparing PFS between patients with positive and negative results was 2.96 (95% CI=2.25-3.89). The patients in interim (18)F-FDG PET negative group had a higher CR rates than that in interim (18)F-FDG PET positive group (RR=5.53, 95% CI=2.59-11.80). Consistent evidence favoring interim (18)F-FDG PET-based treatment assessment should be considered in the management of patients with DLBCL.

  13. A European multicentre and open-label controlled randomized trial to evaluate the efficacy of Sequential treatment with TAcrolimus–Rituximab versus steroids plus cyclophosphamide in patients with primary MEmbranous Nephropathy: the STARMEN study

    Science.gov (United States)

    Rojas-Rivera, Jorge; Fernández-Juárez, Gema; Ortiz, Alberto; Hofstra, Julia; Gesualdo, Loreto; Tesar, Vladimir; Wetzels, Jack; Segarra, Alfons; Egido, Jesus; Praga, Manuel

    2015-01-01

    Background Patients with primary membranous nephropathy (MN) and persistent nephrotic syndrome have a high risk of progression to end-stage renal disease. The Ponticelli protocol (steroids with alkylating agents) is the most effective immunosuppressive therapy for this condition, but it has severe adverse effects. Tacrolimus and rituximab have demonstrated efficacy for remission of nephrotic syndrome in MN with a safer profile. However, the published evidence is largely based on small or short-term observational studies, historical cohorts, comparisons with conservative therapy or clinical trials without appropriate control groups, and there is no head-to-head comparison with the Ponticelli protocol. Methods The STARMEN randomized clinical trial will compare the efficacy of sequential tacrolimus–rituximab therapy with a modified Ponticelli protocol (steroids plus cyclophosphamide). The trial will also evaluate the role of antibodies against the M-type phospholipase A2 receptor (anti-PLA2R) and other antibodies as markers of response to treatment and long-term prognosis. Results The trial has already started with 23 patients having been enrolled as of 1 April 2015, an estimated 21.7% of the estimated sample. PMID:26413273

  14. 应用基因表达谱芯片技术研究Rituximab的耐药机制%Preliminary cDNA microarray studies of Rituximab resistance mechanisms

    Institute of Scientific and Technical Information of China (English)

    潘梅芳; 岑洪; 谭晓虹; 王明月

    2015-01-01

    Objective In this study,we aimed to use cDNA microarrays to identify differentially expressed genes and activation or inhibition of signaling pathways that may account for the phenotype of rituximab-resistant cell lines. Methods Rituximab-resistant B-cell non-Hodgkin’s lymphoma cell lines were established,and cDNA microarray analysis was performed on the resistant and parental cell lines. Bioinformatics analysis was carried out using the KEGG database and DAVID software. Results We identified 70 genes that were up-regulated and 42 that were down-regulated in both Jeko-1/R and Raji/R resistant cell lines compared to parental lines. KEGG pathway analysis suggested that the MAPK signaling pathway is significantly more active in Jeko-1/R and Raji/R cells. GO term analysis of differentially expressed genes suggested that rituximab-resistant cells show the characteristics of“anti-apoptosis”,“promoting proliferation”and“blood vessel development”. Conclusion Our results suggest that rituximab resistance is most closely associated with the MAPK signaling pathway,which may act to inhibit apoptosis and promote proliferation and vascular development. These findings provide a theoretical basis for predicting and overcoming rituximab resistance in the clinical setting.%目的:应用基因表达谱芯片技术检测Rituximab耐药细胞株差异表达基因、富集信号通路及相关生物学行为,初步探讨Rituximab的耐药机制。方法成功构建Rituximab耐药B细胞性非霍奇金淋巴瘤细胞株Jeko-1/R和Raji/R,应用基因表达谱芯片技术检测耐药细胞株与亲本细胞株的差异表达基因,用KEGG数据库及DAVID软件进行生物信息学分析。结果在两株Rituximab耐药细胞株中,同为上调和同为下调表达的差异基因分别有70个和42个;KEGG通路分析提示Rituximab耐药细胞与亲本细胞相比,MAPK信号通路呈富集;基因本体论(gene ontology,GO)分析提示耐药细胞生物

  15. 利妥昔单抗耐药淋巴瘤细胞株构建及其表型分析%Development and characterization of a Rituximab-resistant lymphoma cell line

    Institute of Scientific and Technical Information of China (English)

    王文廉; 万里新; 屈中玉

    2015-01-01

    OBJECTIVE To recapitulate various aspects of acquired resistance by developing and characterizing a Rituximab-resistant lymphoma cell line (Daudi-R),and to provide new ideas in combating Rituximab resistance.METHODS For the generation of Daudi-R clones,wide type cells were grown with step-wise increasing concentrations of Rituximab (0.125-128 μtg/mL) in the presence of 10% fresh human serum.The CDC,ADCC and apoptosis inducing abilities of Rituximab were analyzed in both the wide type and resistant lymphoma clones.The expression of CD20 and two membrane-bound complement regulatory proteins (CD55 and CD59) on surface of wild type and resistant lymphoma cells were compared by Flow Cytometry.The amount of intracellular apoptotic regulatory proteins (Bcl-2,Bcl-xl,Bax and Bak) were detected by western blotting analysis.RESULTS Rituximab induced CDC in Daudi-WT cells were respectively (86.4± 4.08) %,(78.79 ± 6.91) % and (62.87 ± 4.12) % at the concentration of 10,2 and 0.4 μg/mL,comparing with (26.23±42.53)%(t=25.08,P<0.001),(24.67±1.49)% (t=15.43,P<0.001)and (17.99±2.33)% (t=18.98,P<0.001) in Daudi-R cells.Cross-linked Rituximab moderately killed resistant clones (16.11 ± 3.50) %,compared with wild type clones (26.11± 2.78)%,t =3.877,P =0.018.The surface CD20 in resistant clones experienced a transient down-regulation in the first 3 days [(0.73±0.07) fold,Dunnett t test I-J=-0.29,SE=0.091,P=0.035] and a recovery until 10 days [(1.18±0.15) fold,Dunnett t test I-J=-0.18,SE=0.091,P=0.169] after the last treatment of Rituximab.The CD55 and CD59 positive subsets in resistant clones were significantly up-regulated from (1.59 ± 0.62)% and (1.39±0.59)% to (90.1±3.74)%(t=-40.49,P<0.001) and (90.33±2.69)% (t=-54.4,P<0.001),respectively.Western blotting results revealed that the expression of two apoptosis inhibitors (Bcl-2 and Bcl-xl) and promoters (Bax and Bak) respectively experienced an obvious up-and down-regulation in Daudi

  16. Temozolomide plus rituximab for elderly with relapsed primary central nervous system lymphoma%替莫唑胺联合利妥昔单抗对复发的老年原发中枢神经淋巴瘤的应用

    Institute of Scientific and Technical Information of China (English)

    Qingfeng Li; Gang Wu; Zhihua Sun; Jinghua Ren

    2011-01-01

    Objective: The aim of our study was to analyze the long-term results of rituximab combined with temozolomide in treatment of elderly patients (> 60 years) with relapsed primary central nervous system lymphoma (PCNSL). Methods: Twelve postoperative elderly patients (> 60 years) were treated between August 2004 and October 2009. Temozolomide 100 mg/m2to 200 mg/m2 days 1 to 7 and 15 to 21 and rituximab 375 mg/m2 days 1,5, 8, 22. The maximum number of rituximab cycles was two. After one or two cycles of this combination, patients with an objective response and an acceptable level of toxicity continued treatment with single agent temozolomide (days 1 to 5, every 28 days). The overall survival was analyzed by using Kaplan-Meier. Results: The overall survival was 9 months. Toxicity was very mild with no grade 3-4 neurotoxicity toxic events. Conclusion: Rituximab combined with temozolomide seems to yields substantial long-term survival with moderate toxicity for the treatment of elderly relapsed PCNSL.

  17. CHOP-like chemotherapy with or without rituximab in young patients with good-prognosis diffuse large-B-cell lymphoma: 6-year results of an open-label randomised study of the MabThera International Trial (MInT) Group

    DEFF Research Database (Denmark)

    Pfreundschuh, Michael; Kuhnt, Evelyn; Trümper, Lorenz;

    2011-01-01

    The MInT study was the first to show improved 3-year outcomes with the addition of rituximab to a CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone)-like regimen in young patients with good-prognosis diffuse large-B-cell lymphoma. Extended follow-up was needed to establish long...

  18. The use of rituximab in newly diagnosed patients with systemic lupus erythematosus: long-term steroid saving capacity and clinical effectiveness

    Science.gov (United States)

    Gracia-Tello, Borja; Ezeonyeji, Amara; Isenberg, David

    2017-01-01

    Background Previous reports indicate that treating patients with lupus (SLE) at or close to the time of diagnosis successfully without using any, or minimal, corticosteroids by using B-cell depletion (BCD) is possible in the short-term. It is not however known whether using BCD is as effective or reduces corticosteroid use in the long-term. We report the long-term (up to 7 years) use of BCD with respect to its steroid-saving capacity and clinical effectiveness in newly diagnosed SLE. Methods Sixteen female patients with SLE were treated at, or shortly after diagnosis, with BCD therapy (BCDT) minimising the routine use of oral steroids. Post-treatment, most patients were given hydroxychloroquine (n=14) and azathioprine (n=10). The British Isles Lupus Assessment Group (BILAG) disease activity index was used for clinical assessment. Serum antidouble-stranded DNA (dsDNA) antibodies, complement (C3), erythrocyte sedimentation rate (ESR), circulating B lymphocytes (CD19+) and total inmmunoglobulins were tested every 2–6 months (average of 4.5 years) (SD 2) post-treatment. Disease activity and steroid requirement were compared with three patients with SLE treated conventionally, each matched for ethnicity, sex, age, clinical features, disease duration at diagnosis and follow-up period. Results All patients given rituximab achieved BCD. The mean number of flares during follow-up (new BILAG A or B) was 2.63 (SD 3) in the BCDT group and 4 (SD 3.6) in the controls (NS, p=0.14). Post-BCDT, mean anti-dsDNA antibody level fell from 1114 U/mL (SD 1699.3) to 194 (SD 346.7) at 18 months (p=0.043), mean serum ESR fell by >70% at 6 months maintained during follow-up and serum C3 level normalised in 8 patients. The mean cumulative prednisolone dose at 60 months for the patients who underwent BCDT (n=11) was 4745.67 mg (SD 6090 mg) vs 12 553.92 mg (SD 12 672 mg) for the controls (p=0.01). Conclusions Early treatment of patients with SLE with BCDT is safe

  19. Internal dosimetry for the radiological protection of the patient in the therapy with I-131; Dosimetria interna para la proteccion radiologica del paciente en la terapia con I-131

    Energy Technology Data Exchange (ETDEWEB)

    Deluca, G.M.; Rojo, A.M. [Autoridad Regulatoria Nuclear, Av. Del Libertador 8250 (C1429BNP), Buenos Aires (Argentina)]. e-mail: gdeluca@cae.arn.gov.ar

    2006-07-01

    In the patients with differentiated thyroid cancer (CADIT) subjected to therapy with radiopharmaceuticals should be considered the possible risk of sharp depression of the bone marrow like consequence of the intolerance to the quantity of administered activity. The manifestation of the myelotoxicity can limit in a substantial way the future treatments and to deteriorate the predict of resolution of the illness. In this work it shows the physical-mathematical mark of a methodology for the estimated absorbed dose in bone marrow based in the MIRD scheme whose objective is to protect the one patient of the noxious and undesirable effects of the internal radiotherapy in organs that are not target of the same one. The formalism incorporates specific information of the patient and also peculiar characteristics of the internal therapy in patient with CADIT. The considerations are the following ones: (1) the main organ to protect is the bone marrow: (2) the accumulated activity, in bone marrow, it is obtained starting from measurements in blood: (3) the used isotope almost exclusively in this type of therapies is the {sup 131}I; (4) it is used as radiopharmaceutical at the {sup 131}INa that it is characterized to be a simple, inorganic and small molecule: (5) the statistical incidence of the CADIT is bigger in women than in men. It is explained for that it was selected the formalism that is presented, the principles on which it is sustained which are their reaches and their limitations. They are also presented future innovations that can be implemented to effects of improving the estimates. The work is framed inside the thematic of the medical applications of open radioactive sources and it constitutes a contribution to the invigoration of the internal therapy with radiopharmaceuticals. This is due to that the methodology of dose estimation presented supplements with a theoretical biophysics base the protocols of empiric prescription broadly used in this practice. For these reasons, the dosimetric information obtained, adjusted to each concrete case, it contributes to improve the radiological protection of the patient. (Author)

  20. Treatment of solitary, autonomously-functioning, non-toxic thyroid nodules with I131 Adenema tiroideo autónomo no tóxico tratamiento con I131

    Directory of Open Access Journals (Sweden)

    Federico Uribe Londoño

    1991-03-01

    Full Text Available

    Fifteen euthyroid patients (14 women and 1man with solitary autonomously functioning non-toxic thyroid nodules (AFTN were treated with high doses of I131 (mean 19.2 mCi. Diagnosis was made by I131 thyroid scan and triiodothyronine suppression test. The size of the nodule was determined by thyroid ecography both before and after treatment. Evaluation of thyroid function was performed clinically and by T3 T4 and TSH determinations before therapy and during follow.up. AII patients had complete suppression of the surrounding thyroid parenchyma. Two cases of hypothyroidism were found in the first two years of follow-up. We have no explanation for this fact since extranodular thyroid tissue was suppressed and the patients were receiving oral triiodothyronine during radioidine treatment. The nodules decreasedin size In 9 of 13 patients followed (average decrease 45% and disappeared in other 2. our findings suggest that solitary non-toxic AFTN should be treated with I131 particularly if complete suppression of the surrounding thyroid tissue is found. If complete disappearance of the nodule is considered desirable surgical removal must be performed.

    Se trataron 14 mujeres y un hombre, con adenomas tiroideos solitarios funcionalmente autónomos, no tóxicos, con I131 a una dosis promedio de 19.2 mCi. La gamagrafía tiroidea demostró hipercaptación del nódulo con supresión total del resto de la glándula. El tamaño del nódulo se determinó por medio de ecografía tiroidea antes y después del tratamiento, y su autonomía por la prueba de supresión con triyodotironina. El estado tiroideo se puso de presente clínicamente y por la medición de T3, T 4 y TSH en el plasma, antes de la terapia con el radiofármaco y durante la evolución postratamiento. En dos pacientes se presentó hipotiroidismo desde los dos primeros años del período de seguimiento, a pesar de que el tejido tiroideo circundante estaba suprimido y de la administración oral de triyodotironina simultáneamente con el yodo radioactivo. En 13 pacientes se logró hacer seguimiento; en 9 de ellos (69.2% hubo disminución del tamaño del nódulo (promedio de 45%; en dos desapareció y en otros dos no se modificó la lesión. Se sugiere que el tratamiento de los adenomas tiroideos autónomos no tóxicos con I131 es el más apropiado, especialmente si el tejido extranodular está suprimido; ello en vista de la Infrecuencia del hipotiroldismo postratamiento y de la inocultad y facilidad de su administración. Sin embargo, cuando se desea la desaparición total del adenoma y no existen contraindicaciones, debe recurrirse a la cirugía

  1. Dosimetric calculation of I-131 activity for the treatment to patients having differentiated thyroid cancer. Benefits and limitations; Calculo dosimetrico de la actividad de I-131 para tratamiento de pacientes con cancer diferenciado de tiroides (CADT). Beneficios y limitaciones

    Energy Technology Data Exchange (ETDEWEB)

    Cabrejas, R. C.; Chebel, G. M.; Fadel, A. M.; Rojo, A. M.; Deluca, G.; Degross, O. J.; Valdivieso, C. M.; Carbejas, M. L.

    2006-07-01

    Maximum safe activity calculation, that has to be administered for treatment to patients having Differentiated Thyroid Cancer (CADT). No important side effects should be produced. Post treatment evolution was analysed. 23 Dosimetric studies were performed determining blood and whole body uptake curves (CE)during 5 days. Using the MIRDOSE software, the maximum safe activity in the whole body (CE)was calculated. The retained activity in the body (AR), 48 hs. post tracer dose. Should have been less than 2.96 GBq so as to avoid lung fibrosis. 17 patients that received activities<11.1 GBq, had no side effects. Three patients presents special situations: high AR, users in the mouth, and plaque to and leucopenia. This methodology has benefits because AT can be estimated. This was possible for 85% of the patients. When AR was high at 48 hr, AT was diminished to avoid pulmonary lesions. Tumor absorbed dose estimation, will allow the administration of AT>11.1 GBq in the future. (Author)

  2. Dosimetric comparison fixed-individualized activity in the treatment of serious disease with I -131; Comparacion dosimetrica actividad fija-actividad individualizada en el tratamiento de la enfermedad de graves con I-131

    Energy Technology Data Exchange (ETDEWEB)

    Melgar Perez, J.; Orellana Salas, A.; Santaella, Y.; Arrocha Acevedo, J. F.

    2013-07-01

    The iodine-131 therapy has become the treatment with radiopharmaceuticals more frequent in our country, as well as the largest source of exposure to ionizing radiation for members who surround the patient. The aim of this article is to analyse the recommendations of radiological protection which are delivered to the patient receiving radiation discharge, in terms of the duration of the same time, taking into account the radiopharmaceutical dose, the time of entry, the dose rate measured at one meter and the family environment among others. (Author)

  3. Measurement of the Radiation Dose Rates of Patients Receiving Treatment with I-131 Using Telescopic Radiation Survey Meter

    Directory of Open Access Journals (Sweden)

    Yehia Lahfi

    2016-03-01

    Full Text Available Introduction In order to discharge the patients receiving treatment with large radiation doses of 131I for thyroid cancer, it is necessary to measure and evaluate the external dose rates of these patients. The aim of the study was to assess a new method of external dose rate measurement, and to analyze the obtained results as a function of time. Materials and Methods In this study, a telescopic radiation survey meter was utilized to measure the external dose rates of a sample population of 192 patients receiving treatment with high-dose 131I at one, 24, and 48 hours after dose administration. Results The proposed technique could reduce the occupational radiation exposure of the physicist by a factor of 1/16. Moreover, the external dose rates of both genders rapidly decreased with time according to bi-exponential equations, which could be attributed to the additional factors associated with iodine excretion, as well as the physiology of the body in terms of 131I uptake. Conclusion According to the results of this study, telescopic radiation survey meter could be used to measure the external dose rates of patients receiving treatment with 131I. Furthermore, the average difference in the radiation exposure between female and male patients was calculated to be less than 17%.

  4. Analysis of influence of dosimetric factors on the outcome of I-131 therapy in patients with hyperthyroidism

    Energy Technology Data Exchange (ETDEWEB)

    Knapska-Kucharska, M.; Oszukowska, L.; Makarewicz, J. [Department of Nuclear Medecine and Oncological Endocrinology, Province Hospital, Zgierz (Poland); Lewinski, A. [Chair and Department of Endocrinology and Metabolic Diseases, Medical University, Lodz (Poland)

    2012-07-01

    The influence of dosimetric factors on the outcome of {sup 131}I therapy has been examined in hyperthyroid patients submitted to {sup 131}I treatment. The following factors - which could have influence on the effects of therapy with radioiodine - were analysed: the goitre volume, the thyroid radioiodine uptake after 24 h, and the effective half-life time of {sup 131}I (EHL). Five hundred (500) randomly selected patients with hyperthyroidism, treated with {sup 131}I, were studied. They were divided into three groups (based on clinical examination, hormonal and immunological tests, thyroid scintigraphy and ultrasound imaging). The study shows that the effectiveness of {sup 131}I therapy depends on the thyroid volume and absorbed dose in all the groups of patients and on the thyroid radioiodine uptake and EHL in patients with a single autonomously functioning thyroid nodule. We have failed to determine the borderline D, distinguishing between effective and ineffective therapy. The treatment outcome can be predicted with approximately 70% accuracy, based on minimal absorbed dose

  5. Potassium iodide (KI) to block the thyroid from exposure to I-131: current questions and answers to be discussed.

    Science.gov (United States)

    Reiners, Christoph; Schneider, Rita

    2013-05-01

    Thyroid cancer in children and adolescents has to be considered as the most severe health consequence of a nuclear reactor emergency with release of radioiodine into the atmosphere. High doses of potassium iodide are effective to block radioiodine thyroid uptake and to prevent development of thyroid cancer years later. However, there are controversies concerning thyroid cancer risk induced by radioiodine exposure in adults. Further, the interaction of nutritional supply of potassium iodide and radioiodine uptake as well as the interaction of radioiodine with certain drugs has not been addressed properly in existing guidelines and recommendations. How to proceed in case of repeated release of radioiodine is an open, very important question which came up again recently during the Fukushima accident. Lastly, the side effects of iodine thyroid blocking and alternatives of this procedure have not been addressed systematically up to now in guidelines and recommendations. These questions can be answered as follows: in adults, the risk to develop thyroid cancer is negligible. In countries, where nutritional iodine deficiency is still an issue, the risk to develop thyroid cancer after a nuclear reactor emergency has to be considered higher because the thyroid takes up more radioiodine as in the replete condition. Similarly, in patients suffering from thyrotoxicosis, hypothyroidism or endemic goitre not being adequately treated radioiodine uptake is higher than in healthy people. In case of repeated or continued radioiodine release, more than one dose of potassium iodide may be necessary and be taken up to 1 week. Repeated iodine thyroid blocking obviously is not harmful. Side effects of iodine thyroid blocking should not be overestimated; there is little evidence for adverse effects in adults. Newborns and babies, however, may be more sensitive to side effects. In the rare case of iodine hypersensitivity, potassium perchlorate may be applied as an alternative to iodine for thyroid blocking.

  6. Decitabine in Treating Patients With Metastatic Papillary Thyroid Cancer or Follicular Thyroid Cancer Unresponsive to Iodine I 131

    Science.gov (United States)

    2014-08-20

    Recurrent Thyroid Cancer; Stage IVA Follicular Thyroid Cancer; Stage IVA Papillary Thyroid Cancer; Stage IVB Follicular Thyroid Cancer; Stage IVB Papillary Thyroid Cancer; Stage IVC Follicular Thyroid Cancer; Stage IVC Papillary Thyroid Cancer

  7. 活体成像分析异硫氰酸荧光素标记Rituximab在荷淋巴瘤裸鼠体内的生物分布%In vivo imaging analysis of biodistribution of FITC-labeled Rituximab in lymphoma-bearing nude mice

    Institute of Scientific and Technical Information of China (English)

    张胜华; 程昕; 钟根深; 熊冬生; 邵荣光

    2010-01-01

    目的 应用活体动物体内光学成像系统观察抗体药物Rituximab在荷淋巴瘤裸鼠体内的生物分布.方法 制备FITC标记的Rituximab(FITC-Rituximab),用激光扫描共聚焦显微镜和流式细胞仪体外分析FITC-Rituximab与人淋巴瘤Raji细胞的亲和力;建立裸鼠淋巴瘤皮下移植瘤模型,应用活体动物体内光学成像系统观察FITC-Rituximab在荷瘤小鼠体内的分布.结果 流式细胞仪和激光扫描共聚焦显微镜检测证明FITC-Rituximab与淋巴瘤Raji细胞有较好的亲合活性,主要结合在细胞膜表面.体内活体动物光学成像分析表明,FITC-Rituximab在1 h内即可特异性地在肿瘤部位富集,3~4 h即可进入肿瘤组织内部并达到最大浓度富集,8~10 h后在肿瘤组织仍可观察到FITCRituximab的特异性的富集,而在其他组织器官没有可见的荧光存在;双侧皮下移植瘤模型再次证明FITC-Rituximab具有对CD20抗原过表达的淋巴瘤特异性结合能力.结论 动物活体成像系统能够准确地监测FITC标记Rituximab在荷瘤裸鼠体内的动态分布情况,该技术对实时分析抗体药物在荷瘤小鼠体内的靶向效果具有参考价值和指导意义.%Objective To conduct an in vivo optical imaging analysis of the biodistribution of antibody Rituximab in lymphoma tumor-bearing nude mice. Methods Laser scanning confocal microscope and flow cytometry were employed to determine the affinity of FITC-labeled Rituximab (FITC-Rituximab)with human lymphoma Raji cells. And the in vivo optical imaging system was used to analyze the biodistribution of FITC-Rituximab in lymphoma-transplanted xenograft nude mice. Results The results of flow cytometry and laser scanning confocal microscope demonstrated that FITC-Rituximab had remarkable affinity with lymphoma Raji cells and was mainly bound at cell membrane. The results of in vivo imaging analysis suggested that FITC-Rituximab could specifically accumulated at peritumor tissue less

  8. 特异性前哨淋巴结显像剂99Tcm-rituximab药盒的制备及生物评价%Preparation and Evaluation of a Freeze-dried Kit of 99Tcm-rituximab for Sentinel Lymph Node Imaging

    Institute of Scientific and Technical Information of China (English)

    李艳; 李囡; 翟士桢; 王雪鹃; 杨志

    2011-01-01

    采用2-巯基乙醇修饰Rituximab(利妥昔单克隆抗体),制得其冻干药盒.所制得的冻干药盒性质稳定,可在-20℃冷冻保存3个月以上.利用99Tcm-葡庚糖酸钠(GH)交换法,标记冻干药盒得到99Tcm-rituximab,标记率和放化纯度均大于90%.生物分布结果显示:SD大鼠经前脚掌皮下注射99Tcm-rituximab后,前哨淋巴结的摄取值在1~4 h内逐渐增加,在4h时达到(2.14±0.46)%ID,前哨淋巴结与注射点的放射性摄取比在4h时达到最大(14.80%±2.11%),且在18h时,这一比值基本保持不变.SPECT显像结果表明,在30 min~18 h内,大鼠的前哨淋巴结清晰可见,无次级淋巴结显影.本研究提供了一种特异性前哨淋巴结显像剂的药盒化制备方法,该方法操作简便,性能稳定,便于在临床推广应用.%99Tcm-rituximab has been demonstrated to be having favourable properties for sentinel lymph node imaging. The aim of this research was to develop the formulation of the 99Tcm-rituximab freeze-dried kit. Firstly the rituximab was modified by 2-Mercapitoethanol, with the glucose as the excipient, and 1 mL phosphate buffers to compose the kit, which was dispensed into nitrogen-filled vials and aliquots frozen at - 20 ℃. 99Tcm-Rituximab was prepared from the 99Tcm-glucose via ligand exchange method. Both of the labeling yield and the radiochemical purity were more than 90%. The results of biodisdistribution of 99Tcm-rituximab in normal rat with front pad injection showed that the accumulation of the sentinel lymph node increased from 1 h (0. 93±0. 39%ID) to 4 h (2.14±0. 46%ID). The ratio of the uptake of sentinel lymph node to that of the injection site was 14. 80 + 2. 11% at 4 h, with no significant change at 18 h (13. 03% ±3. 98%). The SPECT imaging in rat showed that the sentinel lymph node can be seen clearly without the secondary lymph node imaging 30 min~18 h p. I.. In general, the frozen kit of rituximab was feasible to prepare the sentinel imaging

  9. Image-Based Assessment and Clinical Significance of Absorbed Radiation Dose to Tumor in Repeated High-Dose {sup 131}I Anti-CD20 Monoclonal Antibody (Rituximab) Radioimmunotherapy for Non-Hodgkin's Lymphoma

    Energy Technology Data Exchange (ETDEWEB)

    Byun, Byung Hyun; Kim, Kyeong Min; Woo, Sang Keun; Choi, Tae Hyun; Kang, Hye Jin; Oh, Dong Hyun; Kim, Byeong Il; Choen, Gi Jeong; Choi, Chang Woon; Lim, Sang Moo [Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of)

    2009-02-15

    We assessed the absorbed dose to the tumor (Dose tumor) by using pretreatment FDG-PET and whole-body (WB) planar images in repeated radioimmunotherapy (RIT) with {sup 131}I rituximab for NHL. Patients with NHL (n=4) were administered a therapeutic dose of {sup 131}I rituximab. Serial WB planar images after RIT were acquired and overlaid to the coronal maximum intensity projection (MIP) PET image before RIT. On registered MIP PET and WB planar images, 2D-ROIs were drawn on the region of tumor (n=7) and left medial thigh as background, and Dosetumor was calculated. The correlation between Dosetumor and the CT-based tumor volume change after RIT was analyzed. The differences of Dosetumor and the tumor volume change according to the number of RIT were also assessed. The values of absorbed dose were 397.7{+-}646.2cGy (53.0{approx}2853.0cGy). The values of CT-based tumor volume were 11.3{+-}9.1 cc (2.9{approx}34.2cc), and the % changes of tumor volume before and after RIT were -29.8{+-}44.3% (-100.0%{approx}+42.5%), respectively. Dosetumor and the tumor volume change did not show the linear relationship (p>0.05). Dosetumor and the tumor volume change did not correlate with the number of repeated administration (p>0.05). We could determine the position and contour of viable tumor by MIP PET image. And, registration of PET and gamma camera images was possible to estimate the quantitative values of absorbed dose to tumor.

  10. Impact of rituximab on incidence of and risk factors for central nervous system relapse in patients with diffuse large B-cell lymphoma: a systematic review and meta-analysis.

    Science.gov (United States)

    Zhang, Jing; Chen, Bobin; Xu, Xiaoping

    2014-03-01

    The impact of rituximab (R) on the incidence of central nervous system (CNS) relapse of diffuse large B-cell lymphoma (DLBCL) is unclear. We performed a meta-analysis to explore the risk factors and assess the association between R-chemotherapy (R-chemo) and CNS relapse. We searched MEDLINE, PubMed, EMBASE and OVID for eligible studies. Published group statistics were extracted from each study for analysis; individual patient data from each study were not accessed. Fixed- or random-effects models were used to estimate the odds ratio (OR) with a 95% confidence interval (CI). Eight studies were identified. The OR for R-chemo compared with identical chemotherapy was 0.70 (95% CI 0.54-0.91). Stage III/IV (OR 2.25, 95% CI 1.64-3.08), International Prognostic Index (IPI) > 1 (OR 2.62, 95% CI 1.59-4.33), performance status (PS) > 1 (OR 1.67, 95% CI 1.23-2.27), elevated lactate dehydrogenase (LDH) (OR 2.23, 95% CI 1.54-3.22), bone marrow involvement (OR 2.85, 95% CI 1.99-4.07), more than one extranodal involvement (OR 2.61, 95% CI 1.93-3.54), presence of B symptoms (OR 1.87, 95% CI 1.37-2.56) and testicular involvement (OR 3.83, 95% CI 1.84-7.97) were associated with increased risks of CNS relapse. This meta-analysis demonstrated a lower incidence of CNS relapse of DLBCL in the rituximab era. The risk of CNS relapse can be assessed by stage, IPI, PS, LDH, presence of B symptoms, number of extranodal sites, bone marrow and testicular involvement.

  11. 前哨淋巴结显像剂99Tcm-IT-Rituximab的制备及其定位性能%The preparation and localization study of a novel sentinel lymphoscintigraphy agent 99Tcm-IT-Rituximab

    Institute of Scientific and Technical Information of China (English)

    王雪鹃; 杨志; 林保和; 徐冰; 张岩; 张梅颖

    2006-01-01

    目的 研究前哨淋巴结(SLN)显像剂99Tcm-亚氨基噻吩(IT)-美罗华(Rituximab)的标记方法及其定位效应.方法 采用2-IT作为双功能连接剂,制备99TcmIT-Rituximab,确定最佳反应条件,评价标记抗体分子完整性及生物活性.观察比较99Tcm-IT-Rituximab及99Tcm-硫胶体(SC)2种示踪剂在小鼠淋巴结中的定位性能.将99Tcm-IT-Rituximab作为显像剂,对10例乳腺癌患者行乳腺癌SLN动态显像.结果 2-IT与Rituximab连接的最佳物质的量比为10∶1,4℃反应45 min后,每分子抗体螯合上的游离巯基数平均为2.1个.IT-Rituximab分子保持完整、免疫活性保留完全.99Tcm-IT-Rituximab的标记率>90%,其与B淋巴瘤细胞株Raji细胞的结合率为69.4%.动物显像结果显示99Tcm-IT-Rituximab可清晰定位小鼠SLN,注射后30 min~24 h SLN均可显影,2 h后SLN显影清晰,至24 h未见次级淋巴结显影.动物体内分布数据显示99Tcm-IT-Rituximab定位性能明显优于99Tcm-SC,24 h时SLN百分注射剂量率(%ID)为4.49%,次级及第3级淋巴结基本无摄取,24 h注射点滞留率为22.14%.结论 该标记方法简单,标记率高;99Tcm-IT-Rituximab在SLN中定位性能良好,是一种潜在的新型SLN显像剂.

  12. Rituximab对紫杉醇诱导人B淋巴瘤细胞株凋亡的增敏作用%Rituximab-mediated Sensitiziation of B-NHL Cell Lines to Apoptosis Induced by Paclitaxel

    Institute of Scientific and Technical Information of China (English)

    张红雨; 管忠震; 黄岩; 张星; 林桐榆

    2008-01-01

    目的 基于对CHOP(gg磷酰胺、阿霉素、长春新碱和强的松)联合化疗方案治疗侵袭性淋巴瘤疗效的不尽人意,本文研究利妥昔单抗(Rituximab)对新一代化疗药物Paclitaxel的化疗增敏作用,并探讨其可能的作用机制.方法 (1)体外培养Caudi、Ramos、Namalwa和Raji细胞,采用XTT法测定细胞增殖抑制率:以药物浓度为横坐标.抑制率为纵坐标绘出细胞增殖抑制曲线,比较单药和两药协同作用曲线,若联合作用曲线左移表示有协同作用,右移表示有拮抗作用.(2)Western blot测定:Daudi、Ramos、Raji和Na-malwa细胞经Rituximab 20μg/ml作用24小时后检测抗凋亡蛋白Bcl.2的表达情况.结果 (1)XrT法测定Paclitaxel单药及与Rituximab联合作用对各细胞株增殖抑制率:对Daudi、Namalwa、Ramos和Raji细胞株,Rituximab对Paclitaxel的细胞毒作用有明显的增敏作用;(2)Western blot测定:在Namalwa和Raji细胞株中,经Rituzdmab作用24小时后,可见Bcl.2蛋白表达下调.结论 (1)单药Rituximab对Paclitaxel有明显的化疗增敏作用.(2)在Namalwa和Rail细胞株,经Rituximab作用24小时后可见Bcl-2表达下调,可能是Rituximab增敏的机制之一.

  13. 前哨淋巴结显像剂99Tcm-rituximab体外特性和安全限度的实验研究%Experimental Study of Biological Property and Safety Limitation of Sentinel Lymph Node Imaging Agent 99Tcm-rituximab

    Institute of Scientific and Technical Information of China (English)

    王雪鹃; 张岩; 李艳; 翟士桢; 林保和; 杨志

    2011-01-01

    用99Tcm标记rituximab(美罗华)评价特异性前哨淋巴结(SLN)示踪剂99Tcm-rituximab体外特性及其体内应用的安全性.采用聚丙烯酰胺凝胶电泳(SDS-PAGE)检测了99Tcm-Rituximab的分子完整性;采用间接酶联免疫荧光分析(ELISA)及流式细胞术检测了99Tcm-rituximab的免疫活性;最后依据中华药典的要求行99Tcm-Rituximab安全限度及在正常小鼠体内分布实验.结果显示:99Tcm- rituximab标记率为90%~95%;标记化合物分子完整,免疫活性保留完全,标记化合物无菌无热源.受试小鼠以60 mg/kg剂量注射99 Tcm-rituximab(相当于人体用量的500倍),1周内未见小鼠死亡.小鼠体内分布结果显示:99Tcm-rituximab入血后主要通过肾脏排泄,放射性摄取值由1h的(14.01±0.61)%ID/g减少为24 h的(3.51±0.48)% ID/g;肝脏亦可见摄取.各器官未见有明显的放射性滞留.因此,99Tcm-rituximab结构及性能稳定,无急性毒性,使用安全,可应用于临床.%To evaluate the biological property and safety limitation of a specific sentinel lym-phoscintigraphy imaging agent, 99Tcm-rituximab, 99Tcm-rituximab were analyzed for chemical and radiochemical purity, via SDS-PAGE and ITLC-SG. The immunoreactivity were detected via ELISA and flow cytometry. The safety limitation and biodistribution were tested according to the Chinese Pharmacopeia. The results showed that 99Tcm-rituximab, with a labeling yield of 90%~95%, was intact, and processed similar immunoreactivity of ritux-imab. The final product was bacteria and pyogen free, and was safe to the body. According to the data of biodistribution, most of agent was excreted by the kiney, and the radio uptake decreased from (14. 01±0. 61)%ID/g at 1 h to (3. 51+0. 48) %ID/g at 24 h. The liver also uptook the agent. No accumulation was found in the normal tissue. 99Tcm-rituximab is stable and contains a good immunoreacivity and can be effectively used for clinical study.

  14. Validation of prospective whole-body bone marrow dosimetry by SPECT/CT multimodality imaging in {sup 131}I-anti-CD20 rituximab radioimmunotherapy of non-Hodgkin's lymphoma

    Energy Technology Data Exchange (ETDEWEB)

    Boucek, Jan A. [Fremantle Hospital, Department of Nuclear Medicine, Fremantle (Australia); Turner, J. Harvey [Fremantle Hospital, Department of Nuclear Medicine, Fremantle (Australia); University of Western Australia, School of Medicine and Pharmacology (Australia)

    2005-04-01

    Radioimmunotherapy (RIT) for relapsed non-Hodgkin's lymphoma is emerging as a promising treatment strategy. Myelosuppression is the dose-limiting toxicity and may be particularly problematic in patients heavily pretreated with chemotherapy. Reliable dosimetry is likely to minimise toxicity and improve treatment efficacy, and the aim of this study was to elucidate the complex problems of dosimetry of RIT by using an integrated SPECT/CT system. As a part of a clinical trial of {sup 131}I-anti-CD20 rituximab RIT of non-Hodgkin's lymphoma, we employed a patient-specific prospective dosimetry method utilising the whole-body effective half-life of antibody and the patient's ideal weight to calculate the administered activity for RIT corresponding to a prescribed radiation absorbed dose of 0.75 Gy to the whole body. A novel technique of quantitation of bone marrow uptake with hybrid SPECT/CT imaging was developed to validate this methodology by using post-RIT extended imaging and data collection. A strong, statistically significant correlation (p=0.001) between whole-body effective half-life of antibody and effective marrow half-life was demonstrated. Furthermore, it was found that bone marrow activity concentration was proportional to administered activity per unit weight, height or body surface area (p<0.001). The results of this study show the proposed whole-body dosimetry method to be valid and clinically applicable for safe, effective RIT. (orig.)

  15. Clinical study of low dose rituximab for the therapy in elderly patients with chronic refractory immune thrombocytopenia%小剂量利妥昔单抗治疗老年慢性难治性免疫性血小板减少症的临床研究

    Institute of Scientific and Technical Information of China (English)

    郭素丽; 陈娜飞; 魏秋平; 陈铁虎

    2013-01-01

    Objective To study the efficacy and safty of low dose rituximab therapy in elderly patients with chronic refractory immune thrombocytopenia(ITP) .Methods 36 elderly patients with chronic refractory ITP were collected from Xingtai People′s Hospital of Hebei ,the patients were given intravenous injection of intravenous rituximab at the dose of 100 mg once weekly for 4 consecutive weeks ,observing the efficacy and adverse reaction and following up for 12 months .Difference of platelet (PLT ) ,white blood cell (WBC) ,cluster differentiation 8 + (CD8 + ) ,CD19 + eukomonocyte number and immunoglobulin (IgG ,IgM ,IgA )were compared before and after treatment .Results The responses of complete remission (CR)were 17 casese(47 .2% ) ,remission (R) were 11 casese (30 .6% ) and no remission (NR) 8 casese (22 .2% ) respectively ,2 patients experienced mild dizziness and chest tightness ;PLT were significantly increased ( P = 0 .001) after treatment ,CD19 + lymphocyte count decreased significantly (P =0 .001) ,WBC ,CD8 + lymphocyte and serum immunoglobulin IgG ,IgM ,IgA showed no significant difference before and after treat-ment(P> 0 .05) .Conclusion Low dose rituximab had better clinical efficacy for the treatment of elderly patients with chronic re -fractory ITP ,low dose rituximab may be a effective treatment in elderly chronic refractory ITP patients with minor adverse reac -tions .%目的:研究小剂量利妥昔单抗(rituximab)治疗老年慢性难治性免疫性血小板减少症(ITP)的疗效和安全性。方法收集河北省邢台市人民医院血液科36例老年慢性难治性 ITP 患者,静脉注射 rituximab 100 mg ,每周1次,共4周。观察疗效和不良反应,随访12月。比较治疗前后血小板(PLT )、白细胞(WBC)、白细胞分化抗原8+(CD8+)、CD19+淋巴细胞数和免疫球蛋白(IgG ,IgM ,IgA )的区别。结果治疗后患者完全反应(CR)17例(47.2%),有效(R)11例(30.6

  16. 含美罗华联合方案治疗复发耐药B细胞性非霍奇金淋巴瘤%Preliminary outcome of rituximab-containing salvage regimens on relapsed or refractory B-cell non-Hodgkin's lymphoma: single institution experience

    Institute of Scientific and Technical Information of China (English)

    王步飞; 黄慧强; 卜庆

    2006-01-01

    Objective: The prognosis of relapsed or refractory B-cell lymphoma is poor, with a short-term survival after conventional second-line chemotherapy. Rituximab, a chimeric anti-CD20 antigen, in combination with CHOP or CHOP-like chemotherapy may improve both disease free survival (DFS) and overall survival (OS) of naive patients, but its role in the second-line therapy for relapsed non-Hodgkin's Lymphoma (NHL) remains to be defined. This study aimed to evaluate the efficacy of rituximab-containing salvage regimens for relapsed or refractory NHL, and observe the toxicities. Methods: The clinical data of 54 patients, who were with relapsed or refractory NHL and treated in the Cancer Center of Sun Yat-sen University, were analyzed retrospectively. Of the 54 patients, 29 were man, 25 were women, with a median age of 52.5 years old (range 18 to75); 50 patients (92.6%) scored 0-1 for the ECOG performance status; for second-line international prognostic index (slPI), 21(38.9%) scored 0-1, 30 (55.6%) scored 2 to 3, and 3 (5.6%) scored 4-5; 40 cases were diffuse large B-cell lymphoma (DLBCL),accounting for 74.1% of all subtypes. Rituximab was administered intravenously at a dose of 375 mg/m2 at the day before each chemotherapy cycle. The second or third-line salvage regimens included EPOCH, CHOP, DHAP, DICE, IVAC, IMVP-16 and FND. Results: Of the 54 patients, 49 received retuximab-containing salvage regimens. The objective response rate of the 45 evaluable cases was 68.8%, with a complete remission (CR) rate of 37.7%; 3 patients achieved CR after radiotherapy following rituximab-based regimens and 3 achieved CR after autologous hematopoietic stem cell transplantation. The most frequent adverse events were leucopenia, nausea and alopecia. The addition of rituximab to chemotherapy only elevated the occurrence of mild infusion-related reactions, such as chills, fever and pruritus. The median follow-up time was 18 months (range 2-86 months); 5 patients were lost, 24 were dead (23

  17. 利妥昔单抗联合化疗治疗B细胞淋巴瘤后乙肝病毒激活情况的回顾性研究%Retrospective analysis of hepatitis B virus reactivation after rituximab combination chemotherapy in patients with B-cell lymphoma

    Institute of Scientific and Technical Information of China (English)

    Yun Fan; Chong Luo; Luhong Luo; Zhiyu Huang; Haifeng Yu

    2011-01-01

    Objective: The aim of the study was to investigate the reactivations of hepatitis B virus (HBV) after rituximabcontaining chemotherapy in patients with B-cell lymphoma with surface antigen of hepatitis B virus (HBsAg)-positive, or hepatitis B core antibody (HBcAb)-positive. Methods: A retrospective study of HBV-related markers was performed before and after rituximab-containing treatment in 189 consecutive patients with CD20-positive B-cell lymphoma. Results: Among the 189 non-Hodgkin's lymphoma (NHL) patients who received rituximab combination chemotherapy, 31 (16.6%) were HBsAg positive and 82 (43.9%) HBsAg negative/HBcAb positive, and 76 were HBsAg and HBcAb negative. Of the 31 HBsAg positive patients, 3 (9.7%) experienced reactivation of HBV. The prevalence of HBV reactivation was 4.0% (1/25) in patients who received prophylactic antiviral treatment and 33.3% (2/6) in those who did not receive prophylactic antiviral treatment (P =0.032). Prophylactic antiviral treatment decreased the rate of HBV reactivation. Among the 82 HBsAg negative/HBcAb positive patients, 1 (1.2%) experienced HBV reactivation leading to serious hepatitis. Conclusion: Our experience indicates that rituximab-based therapy may cause serious HBV-related complications and even death in HBsAg-positive patients. Preemptive use of antiviral treatment enabled successful management of HBV reactivation. In HBsAg-negative and HBcAb-positive lymphoma patients the prevalence of HBV reactivation is low (1.2%). Close monitoring HBV until at least 6 months after anticancer therapy is required, prophylactic antiviral therapy needs to be evaluated further.

  18. Health-related quality of life and symptoms in patients with rituximab-refractory indolent non-Hodgkin lymphoma treated in the phase III GADOLIN study with obinutuzumab plus bendamustine versus bendamustine alone.

    Science.gov (United States)

    Cheson, Bruce D; Trask, Peter C; Gribben, John G; Dimier, Natalie; Kimby, Eva; Lugtenburg, Pieternella J; Thieblemont, Catherine; Wassner-Fritsch, Elisabeth; Launonen, Aino; Sehn, Laurie H

    2017-02-01

    We present health-related quality of life (HRQoL) data from GADOLIN, comparing bendamustine (B) alone or combined with obinutuzumab (G-B) in rituximab-refractory indolent non-Hodgkin lymphoma patients. The Functional Assessment of Cancer Treatment-Lymphoma (FACT-Lym) questionnaire was administered on day 1 of cycles 1, 3, and 5 during treatment, at end of induction (EOI), bi-monthly for 2 years during maintenance/follow-up, and annually during extended follow-up until progression/death. Time to first ≥6-point worsening from baseline in the FACT-Lym trial outcome index (TOI) was estimated. Minimally important differences at individual subscale and total score level were used to define the proportion of patients reporting improvement on the FACT-Lym lymphoma-specific subscale (≥3 points), FACT-Lym TOI (≥6 points), and FACT-Lym total score (≥7 points). Overall, 396 patients were randomized. Analysis was conducted when 175 Independent Review Committee-assessed progression-free survival (PFS) events were observed. Questionnaire completion rates were generally balanced between arms at baseline, EOI, and final follow-up. Median time to ≥6-point worsening from baseline on the FACT-Lym TOI was 8.0 months in the G-B arm and 4.6 months in the B arm (HR 0.74; 95% CI 0.56-0.98). More G-B patients reported meaningful improvements on the FACT-Lym questionnaire subscales. Results were similar when follicular lymphoma patients were analyzed separately. The delayed time to worsening and greater proportion of patients reporting meaningful improvement in HRQoL in the G-B arm suggest that benefit in PFS is not at the expense of an increase in treatment-related toxicity that could lead to reduced HRQoL.

  19. Immunoblastic morphology as a possible prognostic indicator for the outcome of the patients with diffuse large B cell lymphoma in era of the rituximab based treatment: single centre experience

    Directory of Open Access Journals (Sweden)

    S. Trajkova

    2013-04-01

    Full Text Available Recently the results from one large prospective study indicated that immunoblastic morphology and not immunohistohemical features predict the outcome of the Diffuse large B lymphoma (DLBL. In order to investigate the prediction value of the immunoblastic morphology (IB as a possible prognostic indicator for the outcome of our DLBL patient treated with the Rituximab (R-CHOP regimen we conducted a retrospective study. Our study enrolled 192 DLBL patients diagnosed and treated at the University Clinic of Hematology in the period between February 2002 and December 2007. They were all treated with R-CHOP regimen and the median follow-up of the patient was 36 months. We analyzed the biopsy samples immunohistochemically for markers of germinal center (BCL6, post-germinal center (MUM1 and apoptosis (BCL2.The patients were categorized as DLBL(132; 68.7%, IB(60; 31.2. The median overall survival time (OS were 59.3 months in DLBL group and 42.2 months in IB group, and time to treatment (TT were 56.8 and 30.6 months respectively for the IB group. The DLBL and IB groups were comparable regarding the age, gender distributions and all others already established prognostic parameters as performance status, advanced IPI, albumin level except for the low IPI 0-2 which was statistically associated with the DLBL group (p=.024. Our results did not show any statistical survival advantage and better outcome for the patient classified as DLBL when treated with R-CHOP and indicate that immunohistohemical markers do not really reflect the molecular diversity of the tumor. Our work shows that IB morphology is a major risk factor in DLBL patients treated with R-CHOP. Therefore this morphology appears to capture some adverse molecular events that a currently hard to detect with routine diagnostic procedures. [Int J Res Med Sci 2013; 1(2.000: 47-52

  20. Biological response of B-cell lymphoma cells in vitro to 131I-rituximab%131I-rituximab对B细胞淋巴瘤细胞生物学效应的实验研究

    Institute of Scientific and Technical Information of China (English)

    魏莉; 罗荣城; 张军一; 严晓; 方永鑫; 费丽华

    2006-01-01

    目的研究131I标记的rituximab对CD20高表达的B细胞淋巴瘤细胞的生物学效应,为放射免疫导向治疗提供实验依据.方法IODO-GEN法将131I标记于抗CD20单抗rituximab,用Annexin V-FITC/PI双染法检测131I-rituximab对Raji细胞的诱导凋亡作用,PI染色法检测细胞周期分布.结果Annexin V-FITC/PI双染法检测凋亡率:131I-rituximab组凋亡率为51.99%,1311I组为42.71%,rituximab组为29.42%,对照组为26.17%.对照组和rituximab组凋亡率明显低于131I组和131I-rituximab组(P<0.05).PI染色法对比各组的凋亡率(亚二倍体峰):131I-rituximab组细胞凋亡率为4.32%,131I组为1.47%,rituximab组为1.39%,对照组仅0.37%,131I-rituximab组凋亡率明显高于其他各组(p<0.05).131I-rituximab组Raji细胞周期发生变化,细胞大部分被阻滞于G1/G2期.结论131I-rituximab能够调控Raji细胞的细胞周期并诱导其凋亡,从而抑制Raji细胞增殖.

  1. Iodination Conditions of Rituximab and Its Biodistribution in Mice%Rituximab的碘标记方法及其在正常小鼠体内的生物分布

    Institute of Scientific and Technical Information of China (English)

    杜延荣; 方红娟; 陈黎波; 李方

    2007-01-01

    采用N-溴代琥珀酰亚胺(NBS)方法对Rituximab(美罗华)进行标记,并优化标记条件.系统考察了反应时间、NBS 用量、反应温度、反应体积、pH值及KI的加入等条件对125I-Rituximab标记率的影响,用ITLC-SG测定标记率和放化纯度.确定最佳条件为:反应时间2~3 min、pH 7.0、室温、反应体积80 μL为反应最优条件.在最佳条件下,5次标记实验标记物的放化纯度为93.9%±1.6%.采用体外结合实验测定储存不同时间131I-Rituximab的免疫活性,结果表明随着131I-Rituximab储存时间的增加免疫活性下降.正常小鼠静脉注射131I-Rituximab后体内分布显示血液中放射性分布较高,并可持续6 d,表明131I-Rituximab体内稳定.异常毒性实验结果表明131I-Rituximab毒性低.

  2. 利妥昔单抗在治疗免疫介导的肾小球肾炎中的应用%Rituximab for the treatment of immune-mediated glomerular diseases

    Institute of Scientific and Technical Information of China (English)

    姜玲(综述); 李世军(审校)

    2015-01-01

    Rituximab ( RTX) is a monoclonal antibody to the CD 20 antigen on B-cells that was initially designed and approved for the treatment of non-Hodgkin′s B-cell lymphoma and has emerged as a potent immunosuppressant for many immune -mediated disea-ses.Given its efficacy , tolerability and safety profile in comparison to more conventional treatment regimens , RTX is rapidly emerging as a critical therapeutic modality for glomerular disease .The paper reviews the role of RTX in the treatment of ANCA-associated vascul-itis, lupus nephritis , mixed cryoglobulinemia , membranous nephropathy , minimal change disease , and focal segmental glomeruloscle-rosis.%利妥昔单抗( Rituximab, RTX)是用于治疗非霍奇金淋巴瘤的抗CD20人/鼠嵌合型单克隆抗体,也是一种有效治疗自身免疫性疾病的药物。其疗效确切,耐受性及安全性较好,已逐渐成为治疗肾小球肾炎的重要药物之一。文中主要对RTX在抗中性粒细胞胞浆抗体( antineutrophil cytoplasmic antibody , ANCA)相关小血管炎、狼疮性肾炎、混合性冷球蛋白血症、膜性肾病、微小病变肾病和局灶节段性肾小球硬化中的应用作一综述。

  3. Anti-tumor efficacy study of the Bruton's tyrosine kinase (BTK) inhibitor, ONO/GS-4059, in combination with the glycoengineered type II anti-CD20 monoclonal antibody obinutuzumab (GA101) demonstrates superior in vivo efficacy compared to ONO/GS-4059 in combination with rituximab.

    Science.gov (United States)

    Yasuhiro, Tomoko; Sawada, Wako; Klein, Christian; Kozaki, Ryohei; Hotta, Shingo; Yoshizawa, Toshio

    2017-03-01

    The activated B-cell diffuse large B-cell-like lymphoma (ABC-DLBCL) correlates with poor prognosis. The B-cell receptor signaling pathway is known to be dysregulated in NHL/CLL and given BTK is a downstream mediator of BCR signaling, BTK constitutes an interesting and obvious therapeutic target. Given the high potency and selectivity of the BTK inhibitor, ONO/GS-4059, it was hypothesized that, the anti-tumor activity of ONO/GS-4059 could be further enhanced by combining it with the anti-CD20 Abs, rituximab (RTX) or obinutuzumab (GA101). ONO/GS-4059 combined with GA101 or RTX was significantly better than the respective monotherapy with tumor growth inhibition (TGI) of 90% for the GA101 combination and 86% for the RTX combination. In contrast, ibrutinib (PCI-32765) combined with RTX did not result in improved efficacy compared with respective monotherapy. Taken together these data indicate that the combination of ONO/GS-4059 with rituximab and particularly obinutuzumab may be an effective treatment for ABC-DLBCL.

  4. Synthesis and Evaluation of Cy7-Rituximab Targeting CD20 Antigen for in vivo Animal Fluorescence Imaging%CD20靶向Cy7-Rituximab分子探针的制备及在小鼠活体荧光成像中的应用

    Institute of Scientific and Technical Information of China (English)

    林新峰; 朱华; 洪业; 杨志

    2013-01-01

    以B淋巴细胞表面CD20抗原靶向的单克隆抗体Rituximab为载体,通过共价键偶联荧光基团菁染料Cy7,获得了新型荧光分子探针Cy7-Rituximab.利用全光谱紫外-可见分光光度仪、SDS-聚丙烯酰胺凝胶电泳和基质辅助激光解析电离飞行时间质谱等对该探针结构进行表征,并通过激光共聚焦显微镜观察了其在弥漫大B细胞淋巴瘤(DLBCL)细胞中的摄取情况.选用BALB/C裸鼠为模型,尾静脉注射Cy7-Rituximab,通过活体荧光成像系统观察了其在小鼠体内的分布情况.研究结果表明,修饰后的Cy7-Rituximab保持了原有抗体的免疫活性.活体荧光成像结果表明,在CD20高表达的脾脏部位监测到该分子探针的特异性浓集.

  5. 标准剂量利妥昔单抗治疗复发难治性原发免疫性血小板减少症的临床研究%Clinical study of standard dose of rituximab for the treatment of refractory primary immune thrombocytopenia

    Institute of Scientific and Technical Information of China (English)

    朱愿超; 王文; 周郁鸿; 王晓敏; 王欣; 王毅丽; 孙桂珍; 侯明

    2011-01-01

    目的 探讨标准剂量利妥昔单抗治疗复发难治性原发免疫性血小板减少症(ITP)的疗效、安全性及治疗前后B细胞、血小板膜糖蛋白特异性自身抗体的变化.方法 利妥昔单抗每周375 mg/m2,静脉滴注,连用4周,治疗31例复发难治性ITP患者,不伴随使用免疫抑制剂、化疗药、抗凝药及激素冲击疗法.监测治疗前后的血常规,血清免疫球蛋白(IgG、IgM、IgA),血小板GPⅡb/Ⅲa和(或)GP Ⅰb/Ⅸ特异性自身抗体及CD3+、CD4+、CD8+、CD19+、CD20+细胞数.结果 12例完全有效,7例有效,12例无效.中位疗效持续时间6(2~48)个月,有效患者4例复发,其余疗效均维持较好.有效患者治疗后血小板自身抗体均转阴.治疗前后外周血血红蛋白、白细胞计数无明显变化,血清IgG、IgM、IgA无明显变化,CD3+、CD4+、CD8+细胞数无明显变化.治疗后CD19+/CD20+细胞明显下降.多数患者耐受好.结论 利妥昔单抗治疗复发难治性ITP疗效肯定,不良反应可以耐受.%Objective To evaluate the efficacy and safety of rituximab on B-lymphocytes and antiplatelet glycoprotein-specific antibodies in patients with refractory primary immune thrombocytopenic (ITP).Methods Thirty-one ITP patients with a median age of 36 years (range 16 -56 years) received solely intravenous rituximab at the dose of 375 mg/m2 once weekly for consecutive 4 weeks. Lab studies included complete blood count, serum concentrations of IgG, IgM and IgA. CD3+ , CD4 + , CD8 + , CD19 + and CD20 +cell numbers were assayed by flow cytometry and anti-platelet glycoprotein-specific antibodies ( GP Ⅱ b/Ⅲ a,GP Ⅰ b/Ⅸ ) were assayed by monoclonal antibody-specific immobilisation of platelet antigens (MAIPA) prior to and following rituximab therapy. The response was evaluated according to the response criteria of international working group of ITP. Results Complete responses were achieved in 12 cases, response in 7 cases,and no response in 12 cases

  6. Rituximab for the Treatment of Refractory Autoimmune Hemolytic Anemia in Children: Report of Two Cases and Literature Review%利妥昔单抗治疗儿童难治性自身免疫性溶血性贫血2例并文献复习

    Institute of Scientific and Technical Information of China (English)

    温贤浩; 管贤敏; 于洁; 宪莹

    2013-01-01

    目的:探讨利妥昔单抗治疗儿童难治性自身免疫性溶血性贫血(AIHA)的疗效、毒副作用.方法:(1)总结2例难治性A1HA患儿的临床表现、实验室检查结果及使用利妥昔单抗治疗前后的情况.(2)对2例患儿选用利妥昔单抗治疗(每次375 mg/m2,每周1次,共4次),随访利妥昔单抗使用后CD20+细胞、血红蛋白等的变化情况,探讨利妥昔单抗治疗儿童AIHA的疗效;同时观察发热、皮疹、感染等毒副作用.结果:2例患儿诊断AIHA后均首先选用糖皮质激素治疗,初期都能显效,但不能长期维持,需长期依赖激素及输血.使用利妥昔单抗治疗后,2例患儿均能显效,其中1例治愈,1例病情反复,最终死于严重贫血.结论:尽管糖皮质激素是治疗AIHA的一线药物,但激素依赖或难治性病例较常见,因此利妥昔单抗已逐渐成为儿童难治性AIHA安全有效的二线治疗药物.%Objective: To investigate the efficacy and side effect of rituximab in the treatment of refractory autoimmune hemolytic anemia (AIHA) in children. Methods: (1) Two cases of refractory AIHA were selected, discussion on the efficacy of glucocorticoid therapy in children with AIHA. Clinical manifestation, laboratory results and therapies before treated with rituximab of the two patients were summarized. (2) Rituximab was given at a dose of 375 mg/(m2 ? w) for four doses. To observe the changes of CD20* cell, hemoglobin, et al. And to investigate the efficacy of rituxumabin the treatment of refractory AIHA. Meanwhile, the side effect was regarded, such as fever, rash, infection, and so on. Results; Glucocorticoid was used as the first line therapy in the two patients who were diagnosed with AIHA. It was effective in the beginning, but it could not lead to maintenance. The two patients in our study needed persistently using steroids and transfusion to maintain the hemoglobin. The effect of rituximab was affirmed in the two cases. One patient was cured, and

  7. 131 I-Rituximab对B细胞淋巴瘤生物学效应的实验研究%Biological response of B-cell lymphoma to 131I-Rituximab

    Institute of Scientific and Technical Information of China (English)

    蔡秋琼; 杜明华; 陈宝安; 钟英; 黄科; 屈海船

    2008-01-01

    目的:研究131I标记的Rituximab对B细胞淋巴瘤细胞的生物学效应以及对荷人Raji细胞移植瘤裸鼠的放射免疫治疗效果,为放射免疫导向治疗提供实验依据.方法:体外培养人B细胞淋巴瘤细胞系Raji细胞,裸鼠皮下接种Raji细胞成瘤,IODO-GEN法将131I标记于Rituximab,将细胞分为131I-Rituximab组、单纯抗体组、单纯核素组及空白对照组4组,流式细胞仪检测各组Raji细胞凋亡和细胞周期;取30只成瘤裸鼠随机分成高、中、低剂量治疗组及单纯抗体组、单纯核素组、空白对照组6组,进行裸鼠的放射免疫治疗研究.每周测量裸鼠荷瘤大小1次,4周后处死裸鼠,取瘤称重,常规病理分析.结果:131I-Rituximab组凋亡率高于其他各组;131I-Rituximab组细胞周期发生变化,大部分被阻滞在G2期.裸鼠各治疗组与对照组比较,肿瘤生长减慢,肿瘤生长抑制率具有剂量时间依赖性,组织病理学检测显示治疗有效.结论:131I-Rituximab能够诱导Raji细胞凋亡并调控细胞周期,而且可特异性地定位于肿瘤组织,发挥放射免疫导向治疗作用,具有潜在的临床应用价值.

  8. In vitro evaluation of {sup 213}Bi-rituximab versus external gamma irradiation for the treatment of B-CLL patients: relative biological efficacy with respect to apoptosis induction and chromosomal damage

    Energy Technology Data Exchange (ETDEWEB)

    Vandenbulcke, Katia; Lahorte, Christophe; Slegers, Guido [Department of Radiopharmacy, Faculty of Pharmaceutical Sciences, Ghent University, Harelbekestraat 72, 9000, Gent (Belgium); De Vos, Filip; Dierckx, Rudi A. [Division of Nuclear Medicine, Ghent University Hospital (Belgium); Offner, Fritz [Department of Hematology, Ghent University Hospital (Belgium); Philippe, Jan [Department of Clinical Chemistry, Ghent University Hospital (Belgium); Apostolidis, Christos; Molinet, Roger; Nikula, Tuomo K. [European Commission, Joint Research Centre, Institute for Transuranium Elements, Karlsruhe (Germany); Bacher, Klaus; De Gelder, Virginie; Vral, Anne; Thierens, Hubert [Department of Anatomy, Embryology, Histology and Medical Physics, Ghent University (Belgium)

    2003-10-01

    External source radiotherapy and beta radioimmunotherapy (RIT) are effective treatments for lymphoid malignancies. The development of RIT with alpha emitters is attractive because of the high linear energy transfer (LET) and short path length, allowing higher tumour cell kill and lower toxicity to healthy tissues. We assessed the relative biological efficacy (RBE) of alpha RIT (in vitro) compared to external gamma irradiation with respect to induction of apoptosis in B chronic lymphocytic leukaemia (B-CLL) and induction of chromosomal damage in healthy donor B and T lymphocytes. The latter was measured by a micronucleus assay. {sup 213}Bi was eluted from a {sup 225}Ac generator and conjugated to CD20 antibody (rituximab) with CHX-A''-DTPA as a chelator. B-CLL cells from five patients were cultured for 24 h in RPMI/10% FCS while exposed to {sup 213}Bi conjugated to CD20 antibody or after external {sup 60}Co gamma irradiation. Binding assays were performed in samples of all patients to calculate the total absorbed dose. Apoptosis was scored by flow cytometric analyses of the cells stained with annexin V-FITC and 7-AAD. Apoptosis was expressed as % excess over spontaneous apoptosis in control. Full dose range experiments demonstrated {sup 213}Bi-conjugated CD20 antibody to be more effective than equivalent doses of external gamma irradiation, but showed that similar plateau values were reached at 10 Gy. The RBE for induction of apoptosis in B-CLL was 2 between 1.5 and 7 Gy. The micronucleus yield in lymphocytes of healthy volunteers was measured to assess the late toxicity caused by induction of chromosomal instability. While gamma radiation induced a steady increase in micronucleus yields in B and T cells, the damage induced by {sup 213}Bi was more dramatic, with RBE ranging from 5 to 2 between 0.1 Gy and 2 Gy respectively. In contrast to gamma irradiation, {sup 213}Bi inhibited mitogen-stimulated mitosis almost completely at 2 Gy. In conclusion, high

  9. Uso de rituximabe em adultos jovens com diagnóstico de artrite idiopática juvenil refratária ao tratamento convencional: relato de 6 casos

    Directory of Open Access Journals (Sweden)

    Ana Paula Sakamoto

    2015-12-01

    Full Text Available Resumo A artrite idiopática juvenil (AIJ é a doença reumática mais frequente na infância. Sem terapia efetiva, os pacientes podem evoluir rapidamente para incapacidade funcional. Recentemente, a depleção dos linfócitos B surgiu como nova abordagem para o tratamento de doenças autoimunes, incluindo a AIJ. Descrevemos seis casos de pacientes com AIJ, acompanhados em um centro de referência em Reumatologia e Reumatologia Pediátrica, submetidos ao tratamento com rituximabe (RTX após refratariedade a três anti-TNF. Os pacientes receberam ciclos de RTX com duas infusões a cada seis meses. A resposta ao tratamento foi avaliada pelo DAS28, HAQ/CHAQ, avaliação global do médico e do paciente. Dos seis pacientes, quatro eram meninas (média de idade de início da doença: 6,1 anos; média de tempo de evolução de doença: 15,1 anos; média de idade ao receber RTX: 21,6 anos. Quatro pacientes pertenciam ao subtipo poliarticular (um fator reumatoide (FR negativo, três FR positivo, um com AIJ subtipo sistêmico com evolução poliarticular e um com artrite relacionada à entesite. Dos seis pacientes, cinco responderam ao tratamento e durante a evolução de 12 meses a resposta clínica foi mantida, embora não sustentada. No entanto, a descontinuação por reações infusionais motivou a suspensão do RTX em dois pacientes. O uso do RTX em AIJ é restrito aos casos refratários a outros biológicos e, mesmo tendo sido feito em um número pequeno de pacientes e de forma tardia, mostrou ser uma opção terapêutica eficaz.

  10. The effect of B-cell depletion therapy on serological evidence of B-cell and plasmablast activation in patients with rheumatoid arthritis over multiple cycles of rituximab treatment.

    Science.gov (United States)

    Cambridge, G; Perry, H C; Nogueira, L; Serre, G; Parsons, H M; De La Torre, I; Dickson, M C; Leandro, M J; Edwards, J C W

    2014-05-01

    B-cell depletion therapy (BCDT) based on rituximab (RTX) induces clinical remission in a majority of seropositive patients with Rheumatoid arthritis (RA). However, all patients eventually relapse. The aim of this study was to determine whether dynamic changes in combinations of serological measures of B-cell activation were associated over up to three cycles of BCDT. We included only RA patients who gave an adequate clinical response, as measured by DAS28. Twenty three patients were studied over 1 cycle, 21 over 2, and 15 over 3 cycles of BCDT. Serum analytes including isotypes of Rheumatoid factors (RhF) and anti-citrullinated protein/peptide antibodies (ACPA), B-cell activating factor (BAFF), serum free light chains (SFLC), soluble CD23 (sCD23), antibodies to tetanus toxoid (TT) and to pneumococcal capsular polysaccharide (PCP) were measured by ELISA at 4 key points in each cycle, namely: Baseline (pre-RTX in each cycle); when B-cell depleted (CD19+B-cells  1.2). SFLC were used as a measure of plasmablast activity. As sCD23 is cleaved from naïve B-cells coincident with attaining CD27 expression, levels were used as a novel measure of maturation of B-cells to CD27+. The most consistent changes between baseline and B-cell depletion within all 3 cycles were in SFLC, sCD23 and IgM-RhF which fell and in BAFF levels which rose. After 3 complete cycles of BCDT, both IgM autoantibodies and IgG-CCP had decreased, BAFF levels were higher (all p < 0.05); other analytes remained unchanged compared with baseline. Dynamic changes in λSFLC, sCD23, IgM-RhF and BAFF were also consistently associated with relapse in patients with longer clinical responses after B-cell return. Incremental rises in sCD23 levels in cycles 2 and 3 were correlated with time to relapse. Repopulation of the periphery after BCDT is initiated by naïve B-cells and precedes relapse. Our study showed that differentiation into plasmablasts, attended by sCD23 and SFLC production and IgM-RhF specificity

  11. Rituximab in treatment of children with frequently relapsed nephrotic syndrome%利妥昔单抗在小儿频复发肾病综合征中的应用

    Institute of Scientific and Technical Information of China (English)

    都娟; 黄建萍; 王硕; 赵晓艳; 肖丽丽

    2014-01-01

    Objective To explore the effect and safety of rituximab (RTX) in children with frequently relapsed nephrotic syndrome.Methods Twelve children (8 male and 4 female) with frequently relapse nephrotic syndrome were treated with RTX.They all showed resistance to various immunosuppressive agents and relapsed when steroid was reduced at 1.5-2.0 mg/kg.All immunosuppressive agents were stopped.Steroid was prescribed at doses of 2 mg/(kg · d),followed by alternate-day dosing (2 mg/kg) after proteinuria was negative for 5 days,and then tapered by 5 mg every 2 weeks until to low dose (< 0.5 mg/kg on alternate day) or discontinued.RTX was administered at a dose of 375 mg/m2 once every week for 3 weeks.Results The patients were followed up for 4-19 months [median (7.79 ± 3.00) months].Proteinuria turned negative on 1-14 d after first RTX treatment.Mean steroid dosages were significantly reduced than before treatment [alternate-day dosing (1.83 ± 1.02) mg/kg vs alternate-day dosing (0.34 ± 0.16) mg/kg,t =3.78,P =0.002].Gingival hyperplasia and Cushing appearance were significantly improved and steroid-induced glaucoma disappeared.The height was significantly increased compared with before treatment [(2.21 ± 1.40) cm/year vs (8.27 ±2.10) cm/year].Six cases had no relapse during follow-up.Another 6 cases relapsed in 5.5-19.0 months.All patients showed CD19 + B lymphocytes depletion after RTX treatment.However,CD19 + recovery could be seen in 5.5-12.0 months.Serum immunoglobulin did not significantly change.None of the patients was found with adverse events.Conclusions RTX can significantly reduce the dosage of steroid or even stop medication in children free of immunosuppressive agents,maintain remission for (7.79 ± 3.00) months,significantly improve the adverse reaction induced by steroid and immune-suppression.Thus,for children with frequently relapsed nephritic syndrome/steroid-dependent nephrotic syndrome who show resistance to immunosuppressive therapies

  12. Sunitinib in Treating Patients With Thyroid Cancer That Did Not Respond to Iodine I 131 and Cannot Be Removed by Surgery

    Science.gov (United States)

    2016-12-26

    Recurrent Thyroid Gland Carcinoma; Stage III Thyroid Gland Follicular Carcinoma; Stage III Thyroid Gland Medullary Carcinoma; Stage IVA Thyroid Gland Follicular Carcinoma; Stage IVA Thyroid Gland Medullary Carcinoma; Stage IVA Thyroid Gland Papillary Carcinoma; Stage IVB Thyroid Gland Follicular Carcinoma; Stage IVB Thyroid Gland Medullary Carcinoma; Stage IVB Thyroid Gland Papillary Carcinoma; Stage IVC Thyroid Gland Follicular Carcinoma; Stage IVC Thyroid Gland Medullary Carcinoma; Stage IVC Thyroid Gland Papillary Carcinoma; Thyroid Gland Oncocytic Follicular Carcinoma

  13. Evaluation of S-values and dose distributions for Y-90, I-131, Ho-166, and Re-188 in seven lobes of the rat liver

    NARCIS (Netherlands)

    Xie, Tianwu; Liu, Qian; Zaidi, Habib

    2012-01-01

    Purpose: Rats have been widely used in radionuclide therapy research for the treatment of hepatocellular carcinoma (HCC). This has created the need to assess rat liver absorbed radiation dose. In most dose estimation studies, the rat liver is considered as a homogeneous integrated target organ with

  14. Improved targeting of 5-[125I/131I]iodo-2‧-deoxyuridine to rat hepatoma by using lipiodol emulsion

    Science.gov (United States)

    Yu, Hung-Man; Yeh, Hsin-Pei; Chang, Tien-Kui; Huang, Kuang-Liang; Chuang, Kuo-Tang; Liu, Ren-Shen; Wang, Shyh-Jen; Hwang, Jeng-Jong; Chi, Kwan-Hwa; Chen, Fu-Du; Lin, Wuu-Jyh; Chen, Chin-Hsiung; Wang, Hsin-Ell

    2006-12-01

    This study aims to assess whether emulsion of [ 125/131I]IUdR and lipiodol (IUdR/LP) can improve delivery of IUdR into hepatoma. MethodsIn vitro release profile of IUdR from IUdR/LP to serum was performed. IUdR/LP was injected into N1-S1 hepatoma-bearing SD rat via hepatic artery and IUdR/normal saline (IUdR/NS) was used for comparison. Biodistribution, autoradiography, imaging and tumor DNA incorporation assay were performed. The radioactive metabolites in plasma and urine were analyzed. Radiation doses to tumor and organs were estimated. ResultsIUdR released from lipiodol into serum was fast. There were longer retention, more DNA incorporation and higher radiation dose of IUdR in the tumor by using IUdR/LP. IUdR/LP deposited deep in the hepatomas. Only free iodide was found in the plasma and urine after injection of IUdR/LP. ConclusionsHepatic artery injection of IUdR/LP emulsion could definitely enhance the tumor cell uptake and incorporation to DNA of *IUdR, prolong the tumor retention time and increase radiation dose to tumor. IUdR/LP may be an effective therapeutic agent for the treatment of hepatic tumors.

  15. Post-surgical use of radioiodine (I-131) in patients with papillary and follicular thyroid cancer and the issue of remnant ablation : A consensus report

    NARCIS (Netherlands)

    Pacini, F; Schlumberger, M; Harmer, C; Berg, GG; Cohen, O; Duntas, L; Jamar, F; Jarzab, B; Limbert, E; Lind, P; Reiners, C; Franco, FS; Smit, J; Wiersinga, W

    2005-01-01

    Objective: To determine, based on published literature and expert clinical experience. current indications for the post-surgical administration of a large radioiodine activity in patients with differentiated thyroid cancer. Design and methods: A literature review was performed and was then analyzed

  16. Iodine I 131 Monoclonal Antibody BC8 Before Autologous Stem Cell Transplant in Treating Patients With Relapsed or Refractory Hodgkin Lymphoma or Non-Hodgkin Lymphoma

    Science.gov (United States)

    2016-06-10

    Recurrent B-Cell Non-Hodgkin Lymphoma; Recurrent Hodgkin Lymphoma; Recurrent T-Cell Non-Hodgkin Lymphoma; Refractory B-Cell Non-Hodgkin Lymphoma; Refractory Hodgkin Lymphoma; Refractory T-Cell Non-Hodgkin Lymphoma

  17. Iodide kinetics and experimental I