183 results
Search Results
2. research paper The efficacy and safety of B-cell depletion with anti-CD20 monoclonal antibody in adults with chronic immune thrombocytopenic purpura.
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Cooper, Nichola, Stasi, Roberto, Cunningham-Rundles, Susanna, Feuerstein, Michael A., Leonard, John P., Amadori, Sergio, and Bussel, James B.
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THROMBOPENIC purpura , *BLOOD cells , *MONOCLONAL antibody probes , *BLOOD diseases , *IMMUNOGLOBULINS , *CLINICAL trials , *SPLENECTOMY - Abstract
Because of its B-cell depleting effect, rituximab has entered clinical trials in several autoimmune conditions. This study assesses the efficacy and safety of rituximab in 57 adults with chronic immune thrombocytopenic purpura (ITP). All patients had platelet counts <30 × 109/l, all had received two or more previous ITP treatments and 31 had undergone splenectomy. Patients received rituximab 375 mg/m2 weekly for 4 weeks. Thirty-one patients (54%) responded, achieving a platelet count >50 × 109/l: 18 achieved a complete response (CR: platelet count >150 × 109/l) and 13 a partial response (PR: platelet count 50–150 × 109/l). Twenty-nine responses occurred within 8 weeks of the first infusion. Sixteen of 18 CR patients (28% overall), including eight who had failed splenectomy, continued in CR after a median of 72·5 weeks; 15 of 16 are >1 year from the first infusion. Only two of 13 maintained a PR. Thirty-three patients experienced grade 1–2 adverse events and one a grade 3 event, but they all completed treatment. Circulating B cells fell to <0·03 × 109/l. No changes in immunoglobulin levels or infectious complications were seen. In summary, rituximab was well tolerated with no immediate complications and induced a lasting, substantial response in 32% of adults with chronic ITP. [ABSTRACT FROM AUTHOR]
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- 2004
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3. research paper Rituximab for chronic recurring thrombotic thrombocytopenic purpura: a case report and review of the literature.
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Yomtovian, Roslyn, Niklinski, Waldemar, Silver, Bernard, Sarode, Ravindra, and Tsai, Han-Mou
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RITUXIMAB , *THROMBOPENIC purpura , *PLASMA exchange (Therapeutics) , *GENETIC mutation , *AUTOANTIBODIES , *ANTINEOPLASTIC agents - Abstract
Deficiency of von Willebrand factor (VWF) cleaving protease ADAMTS13 has been demonstrated to be the proximate cause of a subset of thrombotic microangiopathic haemolytic anaemias (MAHA) typical for thrombotic thrombocytopenic purpura (TTP). ADAMTS13 gene mutations cause the hereditary form; acquired deficiency has been attributed to presence of an autoantibody, which may represent a specific subset of MAHA best termed ‘autoimmune thrombotic thrombocytopenic purpura’. We describe a patient with relapsing TTP because of ADAMTS13 inhibitors, who failed to achieve sustained remission despite therapies with plasma exchange, steroids, vincristine, staphylococcal protein A and splenectomy. The ADAMTS13 inhibitor titre remained elevated and clinical stability was only maintained by plasma exchange every 2–3 d over a period of 268 d. The patient then received rituximab therapy (eight doses of 375 mg/m2 weekly), during which she required five plasma exchanges in the first 10 d, two exchanges in the next 3 weeks, and none thereafter for 450 d and ongoing. The ADAMTS13 inhibitor titre decreased and enzyme activity increased. We compared this case with that of seven previously reported TTP cases also treated with rituximab; experience suggests that rituximab therapy deserves further investigation for patients with either refractory or relapsing TTP caused by ADAMTS13 inhibitors. [ABSTRACT FROM AUTHOR]
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- 2004
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4. research paper Systemic AL amyloidosis due to non-Hodgkin's lymphoma: an unusual clinicopathologic association.
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Cohen, A.D., Zhou, P., Xiao, Q., Fleisher, M., kalakonda, N., Akhurst, T., Chitale, D.A., Moscowitz, C., Dhodapkar, M.V., Teruya-Feldstein, J., Filippa, D., and Comenzo, R.L.
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AMYLOIDOSIS , *LYMPHOMAS , *PLASMA cells , *PROTEIN metabolism disorders , *IMMUNOGLOBULINS , *RITUXIMAB - Abstract
Systemic AL amyloidosis (AL) is a disorder in which light chains form fibrillar deposits, leading to organ dysfunction and death. Rarely, AL has been associated with non-Hodgkin's lymphoma (NHL), although this association has not been well characterized. We report a series of six patients with AL associated with NHL, primarily lymphoplasmacytic lymphoma. Organ involvement was variable, with frequent bulky lymphadenopathy and visceral cavity deposits, but no cardiac involvement. Positron emission tomography scans were negative. Bone marrow and lymph node biopsies showed a mixed population of CD20+ lymphoid and CD138+ plasma cells. Serum free light chains were elevated, and correlated with response to therapy. Immunoglobulin light chain variable region (Ig VL) germline gene use was typical for AL, reflecting previously observed correlations between germline gene use and organ tropism. Five patients received rituximab-based therapies with two responses. Two patients underwent autologous stem cell transplantation with one complete haematological response. Four patients survive at 10–132 months from diagnosis. AL with NHL has distinctive clinical features but employs the same Ig VL gene repertoire as AL with clonal plasma cell dyscrasias. Serial serum free light chain levels are useful for tracking response to therapy. Treatments aimed at both lymphoid and plasma cell components appear warranted. [ABSTRACT FROM AUTHOR]
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- 2004
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5. Position paper on the therapeutic use of rituximab in CD20-positive diffuse large B-cell non-Hodgkin's lymphoma.
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Pettengell, Ruth and Linch, David
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RITUXIMAB , *DRUG therapy , *B cells - Abstract
Summary. The available data on rituximab in combination with chemotherapy confirm that the addition of an independently active biological agent to full-dose standard chemotherapy results in higher rates of complete response, lower rates of relapse, prolonged survival, little additional toxicity and no compromise of the dose intensity of standard chemotherapy regardless of age and risk group. Given the strength of these data, the British Committee for Standards in Haematology believes that rituximab should be available for prescription by UK haematologists and oncologists according to its licensed indication in patients with diffuse large B-cell lymphoma until further data are available to confirm or refute these results. We consider that the use of rituximab with chemotherapy in aggressive lymphoma is cost-effective and that failure to support its introduction will be strongly in conflict with professional and patient opinion. [ABSTRACT FROM AUTHOR]
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- 2003
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6. Papers to be published in forthcoming issues.
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LISTS ,SERUM sickness ,ANEMIA ,GRANULOCYTES ,RITUXIMAB - Abstract
The article offers a list of papers to be published in future issues of the periodical. Included are "Rituximab-induced serum sickness" by R. E. G. Schutgens, "Granulocyte colony-stimulating factor-induced Sweet Syndrome in a healthy donor," by O. Oiso, K. Watanabe, and A. Kawada, and "Recent insights into the pathogenesis of Diamond Blackfan anaemia," by H. T. Gazda and C . A. Sieff.
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- 2006
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7. Lower anti‐spike levels in B‐cell‐depleted patients after convalescent plasma transfusion suggest the need for repeated doses.
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Focosi, Daniele, Senefeld, Jonathon W., Joyner, Michael J., Sullivan, David, Casadevall, Arturo, Bloch, Evan M., and Franchini, Massimo
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CONVALESCENT plasma ,BLOOD transfusion reaction ,COVID-19 ,AUTOIMMUNE hemolytic anemia - Abstract
Patients transfused with at least two CCP units (patients nos 1-4 and patients nos 7 and 8) cleared the virus faster (median 21 days vs 32 days) than patients receiving only one CCP unit (patients nos 5 and 6). Keywords: COVID-19 convalescent plasma; immunocompromised; neutralizing antibodies; rituximab EN COVID-19 convalescent plasma immunocompromised neutralizing antibodies rituximab e22 e24 3 01/16/23 20230115 NES 230115 We read with interest the recent paper by Gachoud et al., shedding light on plasma anti-spike immunoglobulin G (IgG) level kinetics in 36 immunocompromised COVID-19 patients (mostly unvaccinated and seronegative) transfused with plasma at the time of the alpha variant of concern (VOC).[1] Seventeen patients received four 200-ml units of convalescent plasma (CP) over 48 h, while 19 patients received two 200-ml units of two-dose mRNA vaccine plasma [either putatively COVID-19-naïve (VP) or COVID-19-experienced (CP/VP, a.k.a. "hybrid" plasma or VaxCCP)] over 24 h. The authors show that, in 17 patients previously treated with anti-CD20 monoclonal antibodies within the last 12 months, who represent a difficult-to-treat COVID-19 patient population, post-transfusion plasma anti-spike IgG levels are lower than in 19 untreated immunocompromised patients. [Extracted from the article]
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- 2023
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8. Impact of persistent minimal residual disease post-consolidation therapy in children and adolescents with advanced Burkitt leukaemia: a Children's Oncology Group Pilot Study Report.
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Shiramizu, Bruce, Goldman, Stanton, Smith, Lynette, Agsalda‐Garcia, Melissa, Galardy, Paul, Perkins, Sherrie L., Frazer, J. Kimble, Sanger, Warren, Anderson, James R., Gross, Thomas G., Weinstein, Howard, Harrison, Lauren, Barth, Matthew J., Mussolin, Lara, and Cairo, Mitchell S.
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BURKITT'S lymphoma ,CHILDHOOD cancer ,RITUXIMAB ,POLYMERASE chain reaction ,CANCER in adolescence ,CANCER relapse ,PILOT projects ,THERAPEUTICS - Abstract
Patient-specific primers from 10 children/adolescents with Burkitt leukaemia (BL) ± central nervous system disease who were treated with French-British-American/Lymphome Malins de Burkitt 96 C1 plus rituximab were developed from diagnostic blood/bone marrow. Minimal residual disease ( MRD) was assessed by real-time polymerase chain reaction at the end of induction ( EOI) and consolidation ( EOC). Seventy per cent (7/10) and 71% (5/7) were MRD-positive at EOI and EOC, respectively, with no disease recurrences. MRD after induction and consolidation did not predict relapse and subsequent therapy appeared to eliminate MRD. Thus, assessing MRD at a later time point is warranted in future trials to determine its clinical significance. [ABSTRACT FROM AUTHOR]
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- 2015
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9. A phase 2 study of Rituximab-Bendamustine and Rituximab-Cytarabine for transplant-eligible patients with mantle cell lymphoma.
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Armand, Philippe, Redd, Robert, Bsat, Jad, Mayuram, Sangeetha, Giardino, Angela, Fisher, David C., LaCasce, Ann S., Jacobson, Caron, Davids, Matthew S., Brown, Jennifer R., Weng, Li, Wilkins, Jennifer, Faham, Malek, Freedman, Arnold S., Joyce, Robin, and Jacobsen, Eric D.
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RITUXIMAB ,CYTARABINE ,MANTLE cell lymphoma ,STEM cell transplantation ,DISEASE progression ,CYCLOPHOSPHAMIDE ,THERAPEUTICS - Abstract
Chemoimmunotherapy followed by autologous stem cell transplantation ( ASCT) is a standard therapy for transplant-eligible patients with newly diagnosed mantle cell lymphoma ( MCL). The achievement of complete remission ( CR) and minimal residual disease ( MRD) negativity are associated with better outcomes. We tested an induction regimen of rituximab/bendamustine followed by rituximab/high-dose cytarabine ( RB/ RC). This phase 2 study ( NCT01661881) enrolled 23 transplant-eligible patients aged 42-69, of whom 70% were MCL international prognostic index low-risk. Patients received three cycles of RB followed by three cycles of RC. The primary endpoint of the trial was the rate of CR after six cycles of therapy, with a rate of 75% considered promising. 96% of patients achieved a CR/unconfirmed CR after treatment, meeting the primary objective. One patient progressed on study, one declined ASCT in CR, and the remaining 21 underwent successful stem cell collection and ASCT. After a median follow-up of 13 months, the progression-free survival rate was 96%. Among 15 MRD -evaluable patients who completed treatment, 93% achieved MRD negativity after RB/ RC. In conclusion, RB/ RC achieves very high CR and MRD negativity rates in transplant-eligible patients, with a favourable safety profile. RB/ RC warrants further comparative studies, and may become a useful alternative to RCHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone)-based induction regimens in this patient population. [ABSTRACT FROM AUTHOR]
- Published
- 2016
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10. GPIIb/IIIa autoantibody predicts better rituximab response in ITP.
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Feng, Rui, Liu, Xinguang, Zhao, Yajing, Zhu, Yuanyuan, Peng, Jun, Hou, Ming, and Chen, Chunyan
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IDIOPATHIC thrombocytopenic purpura ,RITUXIMAB ,IMMUNOGLOBULINS ,BLOOD platelets ,ANTINEOPLASTIC agents - Abstract
The article discusses the relationship between antibody specificities and efficacy of rituximab in patients with primary immune thrombocytopenia (ITP). The authors discovered that patients with anti-GPIIb/IIIa autoantibodies responded more to rituximab therapy. Autoantibody specificity was found before rituximab therapy using modified monoclonal antibody immobilization of platelet antigen assay.
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- 2018
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11. Progressive multifocal leukoencephalopathy in patients with follicular lymphoma treated with bendamustine plus rituximab followed by rituximab maintenance.
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D'Alò, Francesco, Malafronte, Rosalia, Piludu, Francesca, Bellesi, Silvia, Cuccaro, Annarosa, Maiolo, Elena, Modoni, Anna, Leccisotti, Lucia, Macis, Giuseppe, Mores, Nadia, De Stefano, Valerio, and Hohaus, Stefan
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PROGRESSIVE multifocal leukoencephalopathy ,JOHN Cunningham virus ,LYMPHOPENIA ,RITUXIMAB ,HIGHLY active antiretroviral therapy - Abstract
Progressive multifocal leukoencephalopathy (PML) is a rare fatal disease caused by polyomavirus JC occurring in the context of a deep and prolonged immunosuppression. The onset of PML symptoms occurred during rituximab maintenance in two patients and at the end of maintenance in a third patient. [Extracted from the article]
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- 2020
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12. Rituximab pharmacokinetics in children and adolescents with de novo intermediate and advanced mature B-cell lymphoma/leukaemia: a Children's Oncology Group report.
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Barth, Matthew J., Goldman, Stanton, Smith, Lynette, Perkins, Sherrie, Shiramizu, Bruce, Gross, Thomas G., Harrison, Lauren, Sanger, Warren, Geyer, Mark B., Giulino‐Roth, Lisa, and Cairo, Mitchell S.
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LEUKEMIA in children ,RITUXIMAB ,PHARMACOKINETICS ,CLINICAL trials ,B cell lymphoma ,DISEASES in teenagers ,MEDICATION safety ,CANCER chemotherapy - Abstract
The ANHL01P1 trial was undertaken to determine pharmacokinetics and safety following the addition of rituximab to French- American- British/ Lymphome Malins de Burkitt ( FAB/ LMB96) chemotherapy in 41 children and adolescents with Stage III/ IV mature B-cell lymphoma/leukaemia. Patients received rituximab (375 mg/m
2 ) days −2 and 0 of two induction cycles and day 0 of two consolidation cycles. Highest peak levels were achieved following the second dose of each induction cycle [299 ± 19 and 384 ± 25 μg/ml (Group-B); 245 ± 31 and 321 ± 32 μg/ml (Group-C)] with sustained troughs and t½ of 26-29 d. Rituximab can be safely added to FAB chemotherapy with high early rituximab peak/trough levels and a long t½. [ABSTRACT FROM AUTHOR]- Published
- 2013
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13. Dose‐intense chemoimmunotherapy plus radioimmunotherapy in high‐risk diffuse large B‐cell lymphoma and mantle cell lymphoma: a phase II study.
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Hudson, Kathryn E., Rizzieri, David, Thomas, Samantha M., LeBlanc, Thomas W., Powell, Zachary, Diehl, Louis, Moore, Joseph O., DeCastro, Carlos, and Beaven, Anne W.
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MANTLE cell lymphoma ,RITUXIMAB ,RADIOIMMUNOTHERAPY ,LEUKOCYTE count - Abstract
The article offers information on a study related to dose-intense chemoimmunotherapy and radioimmunotherapy in high-risk diffuse large B-cell lymphoma and mantle cell lymphoma. It notes the three phases of treatment regimen induction 1, induction 2, and consolidation phase. It mentions the that this therapy is effective in patients with high-risk non-Hodgkin lymphoma (NHL) but is toxic.
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- 2019
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14. Survival of patients with mantle cell lymphoma in the rituximab era: Retrospective binational analysis between 2000 and 2020.
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Harmanen, Minna, Hujo, Mika, Sund, Reijo, Sorigue, Marc, Khan, Madiha, Prusila, Roosa, Klaavuniemi, Tuula, Kari, Esa, Jantunen, Esa, Sunela, Kaisa, Rajamäki, Aino, Alanne, Erika, Kuitunen, Hanne, Sancho, Juan‐Manuel, Jukkola, Arja, Rönkä, Aino, and Kuittinen, Outi
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MANTLE cell lymphoma ,OVERALL survival ,RITUXIMAB ,PROGNOSIS ,RETROSPECTIVE studies - Abstract
Summary: Mantle cell lymphoma (MCL) is a rare peripheral B‐cell lymphoma characterised by eventual relapse and progression towards a more aggressive disease biology. With the introduction of rituximab‐ and cytarabine‐based immunochemotherapy regimens, the prognosis of the disease has changed dramatically over the last two decades. To assess the real‐world survival of patients with MCL, we used a population‐based cohort of 564 patients with MCL who were diagnosed and treated between 2000 and 2020. Patient data were collected from seven Finnish treatment centres and one Spanish treatment centre. For the entire patient population, we report a 2‐year overall survival (OS) rate of 77%, a 5‐year OS of 58%, and a 10‐year OS of 32%. The estimated median OS was 80 months after diagnosis. MCL is associated with increased mortality across the entire patient population. Additionally, we assessed the survival of patients after MCL relapse with the aim of establishing a cut‐off point of prognostic significance. Based on our statistical analysis of survival after the first relapse, disease progression within 24 months of the initial diagnosis should be considered as a strong indicator of poor prognosis. [ABSTRACT FROM AUTHOR]
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- 2023
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15. Eltrombopag, low‐dose rituximab, and dexamethasone combination as frontline treatment of newly diagnosed immune thrombocytopaenia.
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Gómez‐Almaguer, David, Colunga‐Pedraza, Perla R., Gómez‐De León, Andrés, Gutiérrez‐Aguirre, César H., Cantú‐Rodríguez, Olga G., and Jaime‐Pérez, José C.
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THROMBOCYTOPENIA ,COMBINATION drug therapy ,DEXAMETHASONE ,RITUXIMAB ,BLOOD platelet disorders - Abstract
The article examines the safety as well as efficacy of triple treatment for immune thrombocytopenia including eltrombopag, low-dose rituximab, and high-dose dexamethasone. Patients who received more dose of dexamethasone bolus either relapsed or failed to achieve a complete response. Limitations and cost-efficiency of this study are also discussed.
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- 2019
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16. Rituximab with chemotherapy in children and adolescents with central nervous system and/or bone marrow-positive Burkitt lymphoma/leukaemia: a Children's Oncology Group Report.
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Goldman, Stanton, Smith, Lynette, Galardy, Paul, Perkins, Sherrie L., Frazer, John Kimble, Sanger, Warren, Anderson, James R., Gross, Thomas G., Weinstein, Howard, Harrison, Lauren, Shiramizu, Bruce, Barth, Matthew, and Cairo, Mitchell S.
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JUVENILE diseases ,DISEASES in teenagers ,RITUXIMAB ,CANCER chemotherapy ,BURKITT'S lymphoma ,CENTRAL nervous system diseases ,BONE marrow ,ONCOLOGY - Abstract
Children and adolescents with Burkitt Lymphoma ( BL) and combined central nervous system ( CNS) and bone marrow involvement still have a poor prognosis with chemotherapy alone. We therefore investigated in children and adolescents with bone marrow (≥25% blasts) and/or CNS-positive Burkitt lymphoma the chemoimmunotherapy combination of rituximab (375 mg/m
2 ) and the standard chemotherapy arm of our previously reported French- American- British ( FAB) Lymphome Malins de Burkitt ( LMB) 96 trial. Central pathological and cytogenetic characterization was also performed. There were 40 evaluable patients with Burkitt histology (25 with leukaemia and 15 with CNS disease ± leukaemia). The chemoimmunotherapy regimen was well tolerated. The incidence of grade III/ IV mucositis during induction cycles with combined chemotherapy and rituximab was 31% and 26%, respectively. The 3-year event-free survival ( EFS)/overall survival ( OS) was 90% (95% confidence interval [ CI], 76-96%) in the entire cohort and 93% (95% CI, 61-99%) in patients with CNS disease. Based on the results of this trial, an international randomized study of FAB/ LMB 96 chemotherapy ± rituximab for high-risk patients is currently under investigation. [ABSTRACT FROM AUTHOR]- Published
- 2014
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17. Characteristics of thrombocytopenia, anasarca, fever, reticulin fibrosis and organomegaly syndrome: a retrospective study from a large Western cohort.
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Maisonobe, Lucas, Bertinchamp, Rémi, Damian, Louise, Gérard, Laurence, Berisha, Mirlinda, Guillet, Stéphanie, Fieschi, Claire, Malphettes, Marion, Fadlallah, Jehane, Hié, Miguel, Dunogué, Bertrand, De Wilde, Virginie, Vandergheynst, Frédéric, Zafrani, Lara, Grall, Maximilien, Saada, Noémie, Garzaro, Margaux, Oksenhendler, Eric, Galicier, Lionel, and Boutboul, David
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CASTLEMAN'S disease ,EDEMA ,THROMBOCYTOPENIA ,LYMPHOPROLIFERATIVE disorders ,SYNDROMES ,FIBROSIS - Abstract
Summary: Idiopathic multicentric Castleman disease (iMCD) is a non‐clonal inflammatory lymphoproliferative disorder of unknown origin. Recently, TAFRO syndrome (thrombocytopenia, anasarca, fever, reticulin fibrosis and organomegaly) emerged as a singular variant of iMCD in Asia and was associated with a severe course and a poor outcome. The present study describes the first large Western cohort of TAFRO syndrome patients (n = 25) meeting the All Japan TAFRO Syndrome Research Group diagnostic criteria. Characteristics of TAFRO patients were compared to iMCD‐not otherwise specified (iMCD‐NOS) patients used as a control group (n = 43). Our results show that despite baseline characteristics in accordance with previously reported series, Western TAFRO syndrome patients do not appear to present with a worse outcome than iMCD‐NOS patients. There were no significant differences between the two groups regarding treatment choice, response to rituximab (71% vs. 67%) or tocilizumab (69% vs. 91%) in TAFRO and iMCD‐NOS, respectively. The two‐year overall survival was above 95% in both groups. Limits of inclusion and exclusion criteria for TAFRO definition are also discussed. Our findings raise the question of the singularity of the TAFRO entity in Western countries. The data should promote further research using unsupervised models to identify markers of disease severity in Western cohorts of iMCD patients. [ABSTRACT FROM AUTHOR]
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- 2022
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18. Primary therapy and relative survival in patients with lymphoplasmacytic lymphoma/Waldenström macroglobulinaemia: a population‐based study in the Netherlands, 1989–2018.
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Amaador, Karima, Kersten, Marie José, Visser, Otto, Brink, Mirian, Posthuma, Eduardus F. M., Minnema, Monique C., Vos, Josephine M. I., and Dinmohamed, Avinash G.
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WALDENSTROM'S macroglobulinemia ,OVERALL survival ,ANTINEOPLASTIC agents ,AGE groups ,RITUXIMAB - Abstract
Summary: It is unclear how treatment advances impacted the population‐level survival of patients with lymphoplasmacytic lymphoma/Waldenström macroglobulinaemia (LPL/WM). Therefore, we assessed trends in first‐line therapy and relative survival (RS) among patients with LPL/WM diagnosed in the Netherlands between 1989 and 2018 (N = 6232; median age, 70 years; 61% males) using data from the nationwide Netherlands Cancer Registry. Patients were grouped into three age groups (<65, 66–75 and >75 years) and four calendar periods. Overall, treatment with anti‐neoplastic agents within 1 year post‐diagnosis gradually decreased over time, following a broader application of an initial watch‐and‐wait approach. Approximately 40% of patients received anti‐neoplastic therapy during 2011–2018. Furthermore, use of chemotherapy alone decreased over time, following an increased application of chemoimmunotherapy. Detailed data among 1596 patients diagnosed during 2014–2018 revealed that dexamethasone‐rituximab‐cyclophosphamide was the most frequently applied regimen; its use increased from 14% to 39% between 2014 and 2018. The 5‐year RS increased significantly over time, particularly since the introduction of rituximab in the early–mid 2000s. The 5‐year RS during 1989–1995 was 75%, 65%, and 46% across the age groups compared to 93%, 85%, and 79% during 2011–2018. However, the survival improvement was less pronounced after 2011. Collectively, the impressive survival improvement may be accounted for by broader application of rituximab‐containing therapy. The lack of survival improvement in the post‐rituximab era warrants studies across multiple lines of therapy to further improve survival in LPL/WM. [ABSTRACT FROM AUTHOR]
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- 2022
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19. Minimal disease assessment in the treatment of children and adolescents with intermediate-risk (Stage III/IV) B-cell non-Hodgkin lymphoma: a children's oncology group report.
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Shiramizu, Bruce, Goldman, Stanton, Kusao, Ian, Agsalda, Melissa, Lynch, James, Smith, Lynette, Harrison, Lauren, Morris, Erin, Gross, Thomas G., Sanger, Warren, Perkins, Sherrie, and Cairo, Mitchell S.
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HODGKIN'S disease ,POLYMERASE chain reaction ,PEDIATRIC diagnosis ,RITUXIMAB ,CLINICAL prediction rules ,CANCER chemotherapy ,HOSPITAL care for cancer patients - Abstract
Children/adolescents with mature B-cell non-Hodgkin lymphoma (B-NHL) have an excellent prognosis but relapses still occur. While chromosomal aberrations and/or clonal immunoglobulin (Ig) gene rearrangements may indicate risk of failure, a more universal approach was developed to detect minimal disease (MD). Children/adolescents with intermediate-risk B-NHL were treated with French-British-American/Lymphome Malins de Burkitt 96 (FAB/LMB96) B4 modified chemotherapy and rituximab. Specimens from diagnosis, end of induction (EOI), and end of therapy (EOT) were assayed for MD. Initial specimens were screened for IGHV family usage with primer pools followed by individual primers to identify MD. Thirty-two diagnostic/staging specimens screened positive with primer pools and unique IGHV family primers were identified. Two patients relapsed; first relapse (4 months from diagnosis) was MD-positive at EOI, the second (36 months from diagnosis) was MD-positive at EOT. At EOI, recurrent rates were similar between the MRD-positive and MRD-negative patients ( P = 0·40). At EOT, only 13/32 patients had MRD data available with one relapse in the MRD-positive group and no recurrences in the MRD-negative group ( P = 0·077). The study demonstrated molecular-disseminated disease in which Ig IGHV primer pools could be used to assess MD. This feasibility study supports future investigations to assess the validity and significance of MD screening in a larger cohort of patients with intermediate-risk mature B-NHL. [ABSTRACT FROM AUTHOR]
- Published
- 2011
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20. Treatment patterns and outcomes of unfit and elderly patients with Mantle cell lymphoma unfit for standard immunochemotherapy: A UK and Ireland analysis.
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Rampotas, Alexandros, Wilson, Matthew R., Lomas, Oliver, Denny, Nicholas, Leary, Heather, Ferguson, Graeme, McKay, Pamela, Ebsworth, Tim, Miller, Jonathan, Shah, Nimish, Martinez‐Calle, Nicolas, Bishton, Mark, Everden, Angharad, Tucker, David, El‐Hassad, Ezzat, Hennessy, Brian, Doherty, Dearbhla, Prideaux, Steve, Faryal, Rehman, and Hayat, Amjad
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MANTLE cell lymphoma ,OLDER patients ,OVERALL survival ,TREATMENT effectiveness ,RITUXIMAB - Abstract
Summary: Mantle cell lymphoma (MCL) presenting in elderly, unfit patients represents a clinical challenge. Front‐line 'attenuated' or low‐intensity immunochemotherapy is often employed, although outcomes are relatively unexplored. We report outcomes of attenuated immunochemotherapy in 95 patients with MCL across 19 centres in the UK and Ireland considered unfit for full‐dose rituximab‐bendamustine or rituximab‐cyclophosphamide, doxorubicin, vincristine, prednisolone (R‐CHOP). Regimens examined were rituximab‐cyclophosphamide, vincristine, prednisolone (R‐CVP) (n = 19), dose‐attenuated R‐CHOP (n = 22), dose attenuated rituximab‐bendamustine (n = 24) and rituximab‐chlorambucil (n = 30). The primary outcome was progression‐free survival (PFS). The secondary outcomes included overall response, overall survival (OS) and toxicity. The median (range) age was 79 (58–89) years and 50% were aged ≥80 years. The median (range) Cumulative Illness Rating Scale‐Geriatric score was 6 (0–24). The median PFS for all patients was 15 months [95% confidence interval (CI) 8·7–21·2) and median OS was 31·4 months (95% CI 19·7–43·2). By multivariable analysis (MVA), the only clinical factor associated with an inferior PFS was blastoid morphology [hazard ratio (HR) 2·90, P = 0·01). Notably, higher treatment intensity (R‐CHOP/R‐bendamustine composite) provided an independently superior PFS compared with R‐CVP/R‐chlorambucil (MVA HR 0·49, P = 0·02). Factors associated with inferior OS by MVA were Eastern Cooperative Oncology Group Performance Status (HR 2·14, P = 0·04), blastoid morphology (HR 4·08, P = 0·001) and progression of disease at <24 months status (HR 5·68, P < 0·001). Overall, survival after front‐line dose‐attenuated immunochemotherapy is unsatisfactory. Clinical trials investigating novel agents such as Bruton tyrosine kinase and B‐cell lymphoma 2 inhibitors in this specific clinical setting are warranted. [ABSTRACT FROM AUTHOR]
- Published
- 2021
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21. A retrospective observational study to evaluate the clinical outcomes and routine management of patients with chronic lymphocytic leukaemia treated with idelalisib and rituximab in the UK and Ireland (RETRO‐idel).
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Eyre, Toby A., Preston, Gavin, Kagdi, Huseini, Islam, Amin, Nicholson, Toby, Smith, Harry W., Cursley, Adam P., Ramroth, Heribert, Xing, Guan, Gu, Lin, Rajakumaraswamy, Nishanthan, and Fegan, Christopher
- Subjects
CHRONIC leukemia ,LYMPHOCYTIC leukemia ,TREATMENT effectiveness ,PHOSPHATIDYLINOSITOL 3-kinases ,RESPIRATORY infections ,RITUXIMAB - Abstract
Summary: Idelalisib (IDL) is an oral first‐in‐class phosphatidylinositol 3‐kinase delta (PI3Kδ) inhibitor approved for chronic lymphocytic leukaemia (CLL) alongside rituximab (R) since 2014. However, little data exist on routine practice. The RETRO‐idel was a protocol‐led, retrospective study of 110 patients [n = 27 front‐line (1L)] who received IDL‐R. The primary end‐point was clinical overall response rate (ORR). The median (range) follow‐up of the whole cohort was 30·2 (0·1–51·9) months. The median (range) age was 72 (48–89) years. Tumour protein p53‐disruption was common [100% 1L, 32·5% relapsed/refractory (R/R)]. The best ORR (intention‐to‐treat) was 88·2% (1L 96·3%, R/R 85·5%). Overall, the median event‐free survival (mEFS) was 20·3 months and time‐to‐next treatment was 29·2 months. The mEFS for 1L patients was 18·7 months and R/R patients was 21·7 months. The 3‐year overall survival was 56·1% (95% confidence interval 45·7–65·3). IDL was discontinued in 87·3% (n = 96). More patients discontinued due to adverse events in the front‐line setting (1L 63·0% vs. R/R 44·6%) and due to progressive disease in R/R patients (20·5% vs. 3·7% in 1L). Lower respiratory tract infection/pneumonia were reported in 34·5% (Grade ≥3, 19·1%), diarrhoea in 30·9% (Grade ≥3, 6·4%), and colitis in 9·1% (Grade ≥3, 5·5%). Overall, these data describe clear efficacy for IDL‐R in routine practice. No new safety signals were identified, although careful management of known toxicities is required. [ABSTRACT FROM AUTHOR]
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- 2021
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22. A phase 3, randomized study of ofatumumab combined with bendamustine in rituximab‐refractory iNHL (COMPLEMENT A + B study).
- Author
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Rummel, Mathias J., Janssens, Ann, MacDonald, David, Keating, Mary‐Margaret, Zaucha, Jan M., Davis, Jaclyn, Lasher, Janet, Babanrao Pisal, Chaitali, Izquierdo, Miguel, and Friedberg, Jonathan W.
- Subjects
NON-Hodgkin's lymphoma ,OVERALL survival ,PROGRESSION-free survival ,RITUXIMAB ,REVIEW committees - Abstract
Summary: The standard of care for indolent non‐Hodgkin lymphoma (iNHL) is rituximab, an anti‐CD20 antibody, with/without chemotherapy. However, multiple relapses are common in these patients. This phase 3, randomized study compared outcomes of a combination of ofatumumab (a second‐generation anti‐CD20 antibody) and bendamustine, with bendamustine alone in patients unresponsive to prior rituximab‐based treatment. Overall, 346 patients were randomized to receive either the combination or bendamustine alone. Bendamustine was given for ≤8 cycles and ofatumumab for ≤12 cycles. The primary end‐point was progression‐free survival (PFS) after 215 protocol‐defined events assessed by independent review committee (IRC). Median IRC‐assessed PFS was 16·7 and 13·8 months in the combination and monotherapy arms respectively [hazard ratio (HR) = 0·82; P = 0·1390]. Median overall survival (OS) was 58·2 and 51·8 months in the combination and monotherapy arms respectively (HR = 0·89, P = 0·4968). The safety profile was consistent with previous reports. Overall, 73% and 80% of patients in the combination and monotherapy arms, respectively, experienced a ≥grade 3 adverse event. The study did not meet its primary end‐point. No significant improvement in PFS and OS was seen with the combination of ofatumumab and bendamustine as compared with bendamustine alone in rituximab‐refractory iNHL (NCT01077518). [ABSTRACT FROM AUTHOR]
- Published
- 2021
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23. Low‐dose fludarabine and cyclophosphamide combined with rituximab in the first‐line treatment of elderly/comorbid patients with chronic lymphocytic leukaemia/small lymphocytic lymphoma (CLL/SLL): long‐term results of project Q‐lite by the Czech CLL Study Group
- Author
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Smolej, Lukáš, Brychtová, Yvona, Cmunt, Eduard, Doubek, Michael, Špaček, Martin, Belada, David, Šimkovič, Martin, Stejskal, Lukáš, Zygulová, Irena, Urbanová, Renata, Brejcha, Martin, Zuchnická, Jana, Móciková, Heidi, and Kozák, Tomáš
- Subjects
CHRONIC leukemia ,LYMPHOCYTIC leukemia ,COMORBIDITY ,CHRONIC lymphocytic leukemia ,CYCLOPHOSPHAMIDE ,FEBRILE neutropenia - Abstract
Summary: Therapeutic options used to be very limited for treatment‐naïve elderly/comorbid patients with chronic lymphocytic leukaemia/small lymphocytic lymphoma (CLL/SLL) before the introduction of chemo‐immunotherapy. Because dose‐reduced fludarabine‐based regimens yielded promising results, the Czech CLL Study Group initiated a prospective observational study to assess safety and efficacy of low‐dose fludarabine and cyclophosphamide combined with rituximab (FCR) in elderly/comorbid patients. Between March 2009 and July 2012, we enrolled 107 patients considered ineligible for full‐dose FCR (median age, 70 years; median Cumulative Illness Rating Scale score, 5; median creatinine clearance, 69 ml/min). Notably, 77% patients had unfavourable biological prognosis [unmutated immunoglobulin heavy‐chain variable‐region gene (IGHV), 74%; deletion 17p, 9%). Fludarabine was reduced to 12 mg/m2 intravenously (iv) or 20 mg/m2 orally on days 1–3 and cyclophosphamide to 150 mg/m2 iv/orally on days 1–3. Grade 3–4 neutropenia occurred in 56% of the patients, but there were serious infections in only 15%. The median progression‐free survival was 29 months, but was markedly longer in patients with mutated IGHV (median 53 months), especially in absence of del 11q or 17p (median 74 months). Low‐dose FCR is a well‐tolerated and effective first‐line regimen for selected elderly/comorbid patients with CLL/SLL with favourable biology. The study was registered at clinicaltrials.gov (NCT02156726). [ABSTRACT FROM AUTHOR]
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- 2021
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24. Long‐term results of the MCL01 phase II trial of rituximab plus HyperCVAD alternating with high‐dose cytarabine and methotrexate for the initial treatment of patients with mantle cell lymphoma.
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Massaro, Fulvio, Stepanishyna, Yana, Manni, Martina, Luminari, Stefano, Galimberti, Sara, Marcheselli, Luigi, Visco, Carlo, Tecchio, Cristina, Stelitano, Caterina, Angrilli, Francesco, Petrini, Mario, Merli, Francesco, and Federico, Massimo
- Subjects
RITUXIMAB ,METHOTREXATE ,CYTARABINE ,STEM cell transplantation ,LYMPHOPROLIFERATIVE disorders ,MANTLE cell lymphoma ,CASTLEMAN'S disease - Abstract
Summary: Mantle cell lymphoma is a rare and incurable lymphoproliferative disorder. In the MCL01 trial, patients were treated with the R‐HCVAD regimen [rituximab plus HyperCVAD (hyperfractionated cyclophosphamide, vincristine, doxorubicin, dexamethasone; R‐CVAD) alternating with high‐dose methotrexate and cytarabine (AM)] for four cycles followed by autologous stem cell transplantation (ASCT) for those who reached only a partial response. After a median follow‐up of 10·5 years, we reported 10‐year progression‐free and overall survival rates of 35% and 61% respectively, with a 10‐years cumulative incidence rate of second malignancies of 10·6%. Mature results of the MCL01 trial confirmed the efficacy of HyperCVAD‐AM as a frontline regimen for younger patients (≤65 years). [ABSTRACT FROM AUTHOR]
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- 2021
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25. Intensive rituximab regimen in immune‐mediated thrombotic thrombocytopenic purpura can circumvent unresponsiveness to standard rituximab treatment.
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Barba, Christophe, Peyre, Marion, Galicier, Lionel, Cathebras, Pascal, Ranta, Dana, Malot, Sandrine, Veyradier, Agnès, and Coppo, Paul
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RITUXIMAB ,THROMBOTIC thrombocytopenic purpura ,IDIOPATHIC thrombocytopenic purpura ,INSTITUTIONAL review boards - Abstract
Intensive rituximab regimen in immune-mediated thrombotic thrombocytopenic purpura can circumvent unresponsiveness to standard rituximab treatment We focused on iTTP patients in clinical remission who failed to display improved ADAMTS13 activity following a standard treatment with rituximab.3 Patients were enrolled prospectively in our registry from January 2012 to July 2018 through the French Reference Center for Thrombotic Microangiopathies network (www.cnr-mat.fr). We report that an intensive rituximab regimen inspired by maintenance regimens of low-grade B-cell lymphomas allows improving ADAMTS13 activity in most cases (>75% of formerly unresponsive patients), with an acceptable safety profile. So far, only single cases previously supported the relevance of this strategy.10,11,12 Of interest, all three patients who did not respond to intensive therapy received a regimen consisting in a twice-a-year infusion of rituximab instead of the two- to three-month infusion regimen typically offered to the other patients. [Extracted from the article]
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- 2021
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26. Fatigue in children and adolescents with immune thrombocytopenia.
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Grace, Rachael F., Klaassen, Robert J., Shimano, Kristin A., Lambert, Michele P., Grimes, Amanda, Bussel, James B., Breakey, Vicky R., Pastore, Yves D., Black, Vandy, Overholt, Kathleen, Bhat, Rukhmi, Forbes, Peter W., and Neunert, Cindy
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IDIOPATHIC thrombocytopenic purpura ,FATIGUE (Physiology) ,TEENAGERS ,QUALITY of life ,PLATELET count - Abstract
Immune thrombocytopenia (ITP), an acquired autoimmune disorder of low platelets and risk of bleeding, has a substantial impact on health‐related quality of life (HRQoL). Patients with ITP often report significant fatigue, although the pathophysiology of this is poorly understood. In this observational cohort of 120 children receiving second‐line therapies for ITP, we assessed reports of fatigue using the Hockenberry Fatigue Scale. Children and adolescents with ITP reported a similarly high level of fatigue with 54% (29/54) of children and 62% (26/42) of adolescents reporting moderate‐to‐severe fatigue. There was no correlation between fatigue and age or gender. Adolescents with newly diagnosed and persistent ITP had higher mean fatigue scores than those with chronic ITP (P = 0·03). Fatigue significantly improved in children and adolescents by 1 month after starting second‐line treatments, and this improvement continued to be present at 12 months after starting treatment. Fatigue scores at all time‐points correlated with general HRQoL using the Kids ITP Tool, but did not correlate with bleeding symptoms, platelet count, or platelet response to treatment. Fatigue is common in children and adolescents with ITP and may benefit from ITP‐directed treatment even in the absence of bleeding symptoms. [ABSTRACT FROM AUTHOR]
- Published
- 2020
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27. Persisting SARS‐CoV‐2 viraemia after rituximab therapy: two cases with fatal outcome and a review of the literature.
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Tepasse, Phil‐Robin, Hafezi, Wali, Lutz, Mathias, Kühn, Joachim, Wilms, Christian, Wiewrodt, Rainer, Sackarnd, Jan, Keller, Martin, Schmidt, Hartmut H., and Vollenberg, Richard
- Subjects
SARS-CoV-2 ,COVID-19 ,VIREMIA ,LITERATURE reviews ,DISEASE progression - Abstract
Summary: SARS‐CoV‐2 infection can cause severe pneumonia (COVID‐19). There is evidence that patients with comorbidities are at higher risk of a severe disease course. The role of immunosuppression in the disease course is not clear. In the present report, we first describe two cases of persisting SARS‐CoV‐2 viraemia with fatal outcome in patients after rituximab therapy. [ABSTRACT FROM AUTHOR]
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- 2020
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28. IgM paraprotein‐associated peripheral neuropathy: small CD20‐positive B‐cell clones may predict a monoclonal gammopathy of neurological significance and rituximab responsiveness.
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Chen, Lucia Y., Keddie, Stephen, Lunn, Michael P., Bomsztyk, Joshua, Vitsaras, Evan, Gupta, Rajeev, and D'Sa, Shirley
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PERIPHERAL neuropathy ,MONOCLONAL gammopathies ,BONE marrow ,CLONE cells ,PLASMA cells - Abstract
Summary: IgM paraprotein‐associated peripheral neuropathy (PN) in patients without overt evidence of lymphoma is a recognised clinical entity of unknown aetiology. Interrogating the bone marrow B‐cell or plasma cell clones underlying paraproteinemic neuropathies may improve our understanding of both pathogenesis and treatment options. This retrospective observational analysis of IgM paraprotein‐associated PN identified five patients with small pathological MYD88 L265P and CD20‐positive B‐cell clones in their bone marrow using multi‐parametric flow cytometry, who have shown durable neurological response to rituximab. We posit that multi‐parametric flow cytometry may be instrumental in identifying the cellular source of the paraprotein in IgM paraprotein‐associated PN, and thus directing appropriate immunomodulatory therapy. Further understanding of these small pathological B‐cell clones may also provide additional insight into mechanisms of monoclonal gammopathy of clinical significance overall. [ABSTRACT FROM AUTHOR]
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- 2020
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29. Rituximab for treatment of autoimmune acquired platelet function disorders: description of two cases of acquired Glanzmann thrombasthenia and one case of acquired delta storage pool disease.
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Alberelli, Maria Adele, Bacci, Monica, Marchetti, Marina, Ferrazzi, Paola, Dragani, Alfredo, Gamba, Sara, Landolfi, Raffaele, Falanga, Anna, Lodigiani, Corrado, and De Candia, Erica
- Subjects
BLOOD platelet disorders ,RITUXIMAB ,BLOOD platelets ,DISEASES ,LEUCOCYTES ,PLATELET-rich plasma - Abstract
Keywords: acquired platelet function disorders; Glanzmann thrombasthenia; delta storage pool disease; immune-mediated platelet disorder; rituximab Management of these disorders, including haemostatic therapies for the control of bleeding, relies on the treatment of the primary disease and/or immunosuppressive treatment, with variable and unpredictable response. In conclusion, we suggest that rituximab should be considered as a second-line treatment in patients with immune-mediated aPFDs when other immunosuppressive treatments have failed in the control of bleeding symptoms and/or in the stable remission of platelet dysfunction. Acquired platelet function disorders, Glanzmann thrombasthenia, delta storage pool disease, immune-mediated platelet disorder, rituximab. [Extracted from the article]
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- 2019
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30. Late relapse in patients with diffuse large B‐cell lymphoma: impact of rituximab on their incidence and outcome.
- Author
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Vannata, Barbara, Conconi, Annarita, Winkler, Jonas, Cascione, Luciano, Margiotta Casaluci, Gloria, Nassi, Luca, Moia, Riccardo, Pirosa, Maria Cristina, Moccia, Alden A., Stathis, Anastasios, Rossi, Davide, Gaidano, Gianluca, and Zucca, Emanuele
- Subjects
DIFFUSE large B-cell lymphomas ,LACTATE dehydrogenase ,LYMPHOMAS ,WESTERN countries - Abstract
Summary: Diffuse large B‐cell lymphoma (DLBCL) constitutes 25–35% of all non‐Hodgkin lymphomas in Western countries. Approximately two thirds of the patients can be cured with standard immuno‐chemotherapy. Most relapses occur within 1–2 years from diagnosis, however, the occurrence of relapses after 5 years or more has been described. We aimed at defining the incidence and clinical features of late relapses. Data of 1113 DLBCL patients were analysed. Among the 196 patients relapsing after a first complete remission, 36 (18% of relapses and 3% of all DLBCLs) experienced a recurrence more than 5 years from diagnosis. Late relapsing patients, in comparison with those relapsing earlier, showed a more favourable risk profile at presentation: normal lactate dehydrogenase levels (P = 0·002), early Ann Arbor stage (P = 0·006) and low International Prognostic Index (P = 0·003). The risk of late relapse was lowered by the introduction of rituximab as part of the front‐line treatment (P < 0·001). Cause‐specific survival (CSS) from the time of relapse was significantly better for late relapsing patients compared to those relapsing early: 5‐year CSS rates were 53% and 31%, respectively (P = 0·033). A trend toward a better overall survival was also observed, with 5‐year rates after relapse of 47% and 25%, respectively (P = 0·054). [ABSTRACT FROM AUTHOR]
- Published
- 2019
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31. Bendamustine plus rituximab in newly‐diagnosed Waldenström macroglobulinaemia patients. A study on behalf of the French Innovative Leukaemia Organization (FILO).
- Author
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Laribi, Kamel, Poulain, Stéphanie, Willems, Lise, Merabet, Fatiha, Le Calloch, Ronan, Eveillard, Jean R., Herbaux, Charles, Roos‐Weil, Damien, Chaoui, Driss, Roussel, Xavier, Tricot, Sabine, Dupuis, Jehan, Dartigeas, Caroline, Bareau, Benoit, Bene, Marie C., Baugier de Materre, Alix, and Leblond, Véronique
- Subjects
RITUXIMAB ,WALDENSTROM'S macroglobulinemia - Abstract
The article focuses on study that evaluated the efficacy and safety of bendamustine plus rituximab (BR) in symptomatic untreated patients with Waldenstr€om macroglobulinaemia (WM). It mentions the results like a patient developed myelodysplastic syndrome after BR initiation and other developed breast cancer.
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- 2019
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32. Long‐term overall‐ and progression‐free survival after pentostatin, cyclophosphamide and rituximab therapy for indolent non‐Hodgkin lymphoma.
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Khashab, Tamer, Hagemeister, Fredrick, Romaguera, Jorge E., Fanale, Michelle A., Pro, Barbara, McLaughlin, Peter, Rodriguez, M. Alma, Neelapu, Sattva S., Fayad, Luis, Younes, Anas, Feng, Lei, Vega, Francisco, Kwak, Larry W., and Samaniego, Felipe
- Subjects
PROGRESSION-free survival ,BONE marrow ,THERAPEUTICS ,MYELODYSPLASTIC syndromes ,FOLLOW-up studies (Medicine) - Abstract
Summary: In a prospective phase II trial, pentostatin combined with cyclophosphamide and rituximab (PCR) induced strong responses and was well‐tolerated in previously untreated patients with advanced‐stage, indolent non‐Hodgkin lymphoma (iNHL). After a median patient follow‐up of more than 108 months, we performed an intent‐to‐treat analysis of our 83 participants. Progression‐free survival (PFS) rates at 108 months for follicular lymphoma (FL), marginal zone lymphoma (MZL) and small lymphocytic lymphoma (SLL) were 71%, 67% and 15%, respectively, and were affected by clinicopathological characteristics. Ten‐year PFS rates for those with beta‐2‐microglobulin levels <2·2 and ≥2·2 mg/l prior to treatment were 71% and 21%, respectively. Patients without bone marrow involvement had 10‐year PFS rates of 72% vs. 29% for those with involvement. At time of analysis, the median overall survival (OS) had not been reached. The OS rate was 64% at 10 years and differed significantly based on histology: 94% for FL, 66% for MZL and 39% for SLL. Long‐term toxicities included 18 (21·7%) patients with second malignancies and 2 (2·4%) who developed myelodysplastic syndrome after receiving additional lines of chemotherapy. Our 10‐year follow‐up analysis confirms that PCR is an effective, robust and tolerable treatment regimen for patients with iNHL. [ABSTRACT FROM AUTHOR]
- Published
- 2019
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33. Response duration and survival shorten after each relapse in patients with follicular lymphoma treated in the rituximab era.
- Author
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Rivas‐Delgado, Alfredo, Magnano, Laura, Moreno‐Velázquez, Miriam, García, Olga, Nadeu, Ferran, Mozas, Pablo, Dlouhy, Ivan, Baumann, Tycho, Rovira, Jordina, González‐Farre, Blanca, Martínez, Antonio, Balague, Olga, Delgado, Julio, Villamor, Neus, Giné, Eva, Campo, Elías, Sancho‐Cia, Juan M., and López‐Guillermo, Armando
- Abstract
Summary: Follicular lymphoma (FL) is an indolent disease characterized by long survival but frequent relapses. Before the introduction of rituximab, the clinical course of these patients showed a shorter response duration (RD) after each relapse. In this study, we analysed if this pattern of shortened responses remains in patients treated in the rituximab era. We selected 348 patients newly diagnosed with FL in two institutions between 2001 and 2014 that received chemoimmunotherapy. After a median follow‐up of 6·3 years, 10‐year progression‐free and overall survivals were 53% and 72%, respectively. All patients received first‐line, 111 second‐line and 41 third‐line treatments, with a 5‐year RD of 62%, 39% and 24%, respectively (P < 0·0001). Variables predicting longer RD after first‐line treatment were normal β2microglobulin, complete remission achievement and maintenance with rituximab. Patients with longer RD after first‐line showed significantly longer RD after second‐line therapy. Autologous stem‐cell transplantation after second‐line therapy did not significantly impact RD. Median survival after first, second and third therapies was not reached, 7·6 and 4·8 years, respectively, whereas relative survival with respect to a sex‐ and age‐matched Spanish population, the decrease in the life expectancy at 10 years was 17%, 45% and 79%, respectively. Thus, RD still shortens after each relapse in patients with FL treated in first line with rituximab combinations. [ABSTRACT FROM AUTHOR]
- Published
- 2019
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34. Maintenance rituximab or observation after frontline treatment with bendamustine‐rituximab for follicular lymphoma.
- Author
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Hill, Brian T., Nastoupil, Loretta, Winter, Allison M., Becnel, Melody R., Cerhan, James R., Habermann, Thomas M., Link, Brian K., Maurer, Matthew J., Fakhri, Bita, Reddy, Prathima, Smith, Stephen D., Mukhija, Dhruvika, Jagadeesh, Deepa, Desai, Amrita, Alderuccio, Juan Pablo, Lossos, Izidore S., Mehra, Pooja, Portell, Craig A., Goldman, Max L., and Calzada, Oscar
- Subjects
RITUXIMAB ,CANCER chemotherapy ,ELECTRONIC publications ,ADVERSE health care events ,VINCRISTINE - Abstract
Summary: Bendamustine (B) with rituximab (R) is a standard frontline treatment for medically fit follicular lymphoma (FL) patients. The safety and efficacy of maintenance rituximab (MR) after BR induction has not been formally compared to observation for FL, resulting in disparate practice patterns. Prospective trials have shown benefit of MR after R‐CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) or R‐CVP (rituximab, cyclophosphamide, vincristine, prednisone), yet recent data from the GALLIUM study comparing outcomes of patients treated with chemotherapy with R or obinutuzumab (G) showed higher than anticipated fatal adverse events with BR/BG. In order to assess the efficacy and tolerability of MR after BR, we retrospectively collected data on 640 newly diagnosed patients treated with FL. We found that patients who achieved partial remission (PR) after ≥4 cycles of BR had improved duration of response (DOR) with MR vs. no maintenance, whereas those in complete remission did not. These findings were confirmed in a validation cohort. In the entire study population, the known fatal adverse event rate after BR was 2·5% and did not significantly differ in those receiving MR versus no maintenance. [Correction added on 14 January 2019, after online publication: The preceding sentence has been corrected in this current version.] Within the limitations inherent to retrospective analysis, these data suggest that FL patients with a PR to BR experience prolongation of remission with MR with an acceptable safety profile. [ABSTRACT FROM AUTHOR]
- Published
- 2019
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35. Prognostic impact of trisomy 21 in follicular lymphoma.
- Author
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Mitsui, Takeki, Yokohama, Akihiko, Koiso, Hiromi, Saito, Akio, Toyama, Kohtaro, Shimizu, Hiroaki, Ishizaki, Takuma, Irisawa, Hiroyuki, Takizawa, Makiko, Saitoh, Takayuki, Murayama, Kayoko, Matsumoto, Morio, Handa, Hiroshi, Hirato, Junko, Kojima, Masaru, Murakami, Hirokazu, and Tsukamoto, Norifumi
- Subjects
DOWN syndrome ,RITUXIMAB ,PROGRESSION-free survival ,MULTIVARIATE analysis ,DISEASE risk factors ,ABNORMALITIES in animals - Abstract
Summary: The chromosomal abnormalities associated with follicular lymphoma (FL) prognosis are not fully elucidated. Here, we evaluated the pattern of chromosomal abnormalities in FL, and clarified the correlations between the cytogenetic features and clinical outcome. Cytogenetic analysis was performed using standard methods of Giemsa‐banding at diagnosis for 201 FL patients admitted to our hospitals between 2001 and 2013. The identified chromosomal abnormalities were: t(14;18)(q32;q21) (59·2%), +X (17·9%), del(6)(q)/‐6 (16·9%), +7 (14·4%), abnormality of 1q12‐21/1q (12·9%), del(13)(q)/‐13 (11·9%), abnormality of 3q27 (10·4%), abnormality of 10q22‐24 (10·0%), +12/dup(12)(q) (10·0%), abnormality of 1p21‐22/1p (9·0%), +18 (9·0%), del(17)(p)/‐17 (5·0%), and a complex karyotype (54·7%). Patients with trisomy 21 had a significantly shorter progression‐free survival (P = 0·00171) and overall survival (OS) (P < 0·001) than those without trisomy 21; additionally, patients with trisomy 21 in the rituximab‐treated cohort also had a significantly shorter OS (P = 0·000428). Multivariate analysis identified trisomy 21 as an independent risk factor in our cohorts with or without t(14;18) (P = 0·015). In conclusion, the presence of trisomy 21 was an independent risk factor for in FL. Chromosomal analysis of FL patients at diagnosis can provide useful information about their expected survival. [ABSTRACT FROM AUTHOR]
- Published
- 2019
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36. Autologous stem cell transplant and combination immunotherapy of rituximab and interferon‐α induces prolonged clinical and molecular remissions in patients with follicular lymphoma.
- Author
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Smyth, Liam, Buckstein, Rena, Pennell, Nancy, Weerasinghe, Rashmi, Cheung, Matthew C., Imrie, Kevin, Spaner, David, Piliotis, Eugenia, Chodirker, Lisa, Reis, Marciano, Ghorab, Zeina, Zhang, Liying, Boudreau, Violet, Miliken, Angela, and Berinstein, Neil
- Abstract
The article informs on a study conducted for analysing the feasibility of chemo-immunotherapy followed by maintenance drug rituximab. It informs that autologous stem cell transplant and combination immunotherapy of drug rituximab and interferon-a induces prolonged clinical and molecular remissions in patients with follicular lymphoma, along with improving their progression-free survival (PFS) and overall survival (OS) in follicular lymphoma.
- Published
- 2019
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37. Ofatumumab is a feasible alternative anti‐CD20 therapy in patients intolerant of rituximab.
- Author
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Chen, Lucia Y., Shah, Raakhee, Cwynarski, Kate, Lambert, Jonathan, McNamara, Christopher, Mohamedbhai, Sajir G., Virchis, Andres, Townsend, William, D'Sa, Shirley, and Ardeshna, Kirit M.
- Abstract
The article informs on a study conducted for analysing the feasibility of ofatumumab drug as an alternative anti-CD20 therapy in patients intolerant of rituximab drug. It informs that infusion-related reactions (IRR) to rituximab occurred among patients; and patients intolerant of rituximab due to IRRs are likely to have a worse outcome in terms of progression-free survival and overall survival. It also mentions that ofatumumab is the feasible alternative for rituximab.
- Published
- 2019
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38. Study of gene polymorphisms as predictors of treatment efficacy and toxicity in patients with indolent non‐hodgkin lymphomas and mantle cell lymphoma receiving bendamustine and rituximab.
- Author
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Cencini, Emanuele, Sicuranza, Anna, Fabbri, Alberto, Ferrigno, Ilaria, Rigacci, Luigi, Cox, Maria C., Raspadori, Donatella, and Bocchia, Monica
- Subjects
HODGKIN'S disease ,MANTLE cell lymphoma ,RITUXIMAB ,LYMPHOMAS ,ANTINEOPLASTIC agents - Abstract
Summary: Bendamustine is used in combination with rituximab (BR) to treat indolent non‐Hodgkin lymphomas (iNHL) and mantle cell lymphoma (MCL). The variability in treatment efficacy and toxicity could be related to single nucleotide polymorphisms (SNPs) in immune response genes. We would like to show a correlation between SNPs and treatment outcome in iNHL and MCL patients receiving BR. We investigated some SNPs that had already been associated with NHL outcome. Samples were genotyped for the IL2 (rs2069762), IL10 (rs1800890, rs10494879), VEGFA (rs3025039), IL8 (rs4073), CFH (rs1065489) and MTHFR (rs1801131) SNPs by allelic discrimination assays. We enrolled 70 patients that received rituximab 375 mg/m2 and bendamustine 90 mg/m2 every 28 days, both as first‐line treatment and ≥ second‐line regimens. Overall response rate was 97·1% (complete response [CR] rate 73·9%). Treatment toxicity included grade 3–4 neutropenia (24/70 patients), infections (21/70 patients; 1/70 grade 3), skin rash (26/70 patients; 2/70 grade 3). After a median follow‐up of 24 months we did find any correlation between the analysed SNPs, CR rate and PFS. However, we demonstrated an association between the SNP in IL2 (rs2069762) and the onset of skin rash (P = 0·0001). Our study suggests a role for cytokine SNPs in bendamustine‐related toxicity, which could represent a promising research field. [ABSTRACT FROM AUTHOR]
- Published
- 2019
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39. A retrospective study of R‐DHAP/Ox for early progressing follicular lymphoma.
- Author
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Ghione, Paola, Cavallo, Federica, Visco, Carlo, Chen, Zhengming, Castellino, Alessia, Tisi, Maria C., Dogliotti, Irene, Nicolosi, Maura, Boccadoro, Mario, Leonard, John P., Vitolo, Umberto, and Martin, Peter
- Subjects
LYMPHOMA treatment ,RITUXIMAB ,DEXAMETHASONE ,CYTARABINE ,CISPLATIN ,OXALIPLATIN ,KAPLAN-Meier estimator ,RETROSPECTIVE studies - Abstract
The article presents a retrospective study which examined the effectiveness of rituximab, dexamethasone, cytarabine, cisplatin/oxaliplatin (R-DHAP/Ox) as treatment for early progressing follicular lymphoma. Also cited are the effectiveness of R-DHAP/Ox against diffuse large B cell lymphoma (DLCBL) with germinal centre subtype, and the use of the Kaplan-Meier method in estimating the subjects' survival probability.
- Published
- 2018
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40. Prognostic factors and primary treatment for Waldenström macroglobulinemia – a Swedish Lymphoma Registry study.
- Author
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Brandefors, Lena, Melin, Beatrice, Lindh, Jack, Lundqvist, Kristina, and Kimby, Eva
- Subjects
WALDENSTROM'S macroglobulinemia ,RITUXIMAB ,HEMOGLOBINS ,DISEASE incidence ,LACTATE dehydrogenase - Abstract
We present a nationwide prospective Swedish registry‐based study of Waldenström macroglobulinaemia (WM), that focuses on incidence and survival in relation to clinical prognostic factors and primary systemic therapies. A total of 1511 patients with WM and lymphoplasmocytic lymphoma (LPL) were registered in the Swedish Lymphoma Registry (SLR) between 1 January 2000 and 31 December 2014. The age‐adjusted incidence of WM/LPL was 11·5 per million persons per year, three times higher than the reported incidence worldwide. Medical records were retrieved for 1135 patients (75%). A retrospective review showed that 981 (86·1%) of these patients fulfilled the World Health Organization diagnostic criteria for WM and these patients were analysed further. The overall survival (OS) improved between two periods – 2000–2006 and 2007–2014 – with a five‐year OS of 61% and 70%, respectively. Significant prognostic factors for OS, evaluated at the time of diagnosis, were age, elevated lactate dehydrogenase level and haemoglobin ≤115 g/l for patients receiving therapy 0–3 months after diagnosis, and age, poor performance status, haemoglobin ≤115 g/l, and female sex in "watch and wait" patients (multivariable analysis). The level of the IgM monoclonal immunoglobulin had no significant prognostic value. Rituximab included in first‐line therapy was associated with improved survival. [ABSTRACT FROM AUTHOR]
- Published
- 2018
- Full Text
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41. The MCL35 gene expression proliferation assay predicts high‐risk MCL patients in a Norwegian cohort of younger patients given intensive first line therapy.
- Author
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Holte, Harald, Beiske, Klaus, Boyle, Merrill, Trøen, Gunhild, Blaker, Yngvild N., Myklebust, June, Kvaløy, Sunniva, Rosenwald, Andreas, Lingjærde, Ole C., Rimsza, Lisa M., Smeland, Erlend B., Scott, David W., and Kolstad, Arne
- Subjects
GENE expression ,MANTLE cell lymphoma ,CYTARABINE ,RITUXIMAB ,CANCER immunology - Abstract
Summary: Patients with mantle cell lymphoma (MCL) generally have a dismal prognosis. Intensified induction treatment with rituximab and high dose cytarabine (R_HDAC), and consolidation with high‐dose therapy with autologous stem cell support has resulted in 10‐year overall survival (OS) higher than 60%. However, the clinical course varies. Diagnostic tools capable of stratifying patients include the MCL International Prognostic Index (MIPI), gene expression‐based proliferation signature, Ki‐67 proliferation index or tumour cell morphology. Here, we tested the performance of a newly developed Nanostring‐based RNA expression‐based proliferation assay (MCL35) on formalin‐fixed paraffin‐embedded tumour tissue from younger patients recruited in or treated according to Nordic MCL protocols compared to the prognosticators listed above. Seventy‐four patients were included and the assay performed well in all cases except four, which had inadequate RNA quality. The patients were evenly distributed in the MCL35 low‐, intermediate‐ and high‐risk categories. MCL35 low‐ and intermediate‐ risk groups had overlapping progression‐free survival (PFS), while patients in the high‐risk category had significantly inferior PFS. Combining MCL35 with MIPI or the MIPI‐C (MIPI with the addition of binary Ki67 score +/−30%) showed a better discrimination than either assessment alone. In conclusion, the MCL35 assay alone or combined with MIPI or MIPI‐C scores can identify patients who still have a dismal outcome despite intensified treatment. [ABSTRACT FROM AUTHOR]
- Published
- 2018
- Full Text
- View/download PDF
42. Bendamustine and rituximab in elderly patients with low‐tumour burden follicular lymphoma. Results of the LYSA phase II BRIEF study.
- Author
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Gyan, Emmanuel, Sonet, Anne, Brice, Pauline, Anglaret, Bruno, Laribi, Kamel, Fruchart, Christophe, Tilly, Hervé, Araujo, Carla, Soubeyran, Pierre, Gonzalez, Hugo, Morineau, Nadine, Nicolas‐Virelizier, Emmanuelle, Ghesquières, Hervé, Salles, Bruno, Bouabdallah, Réda, Orfeuvre, Hubert, Fahri, Jonathan, Couturier, Olivier, Xerri, Luc, and Feugier, Pierre
- Subjects
LYMPHOMAS ,RITUXIMAB ,HEMATOLOGIC malignancies ,ANTINEOPLASTIC agents ,TERTIARY care - Abstract
Summary: The treatment of low‐tumour burden follicular lymphoma (LTBFL) remains a challenge. Rituximab‐based strategies may be improved by adding chemotherapy. This Lymphoma Study Association multicentre phase II study assessed rituximab and bendamustine in 63 patients with untreated LTBFL who were aged over 60 years old and had a follicular lymphoma International Prognostic Index (FLIPI) score ≥2. Induction comprised 4 weekly cycles of rituximab 375 mg/m2 intravenously combined with 2 cycles of bendamustine 90 mg/m2 days 1–2 with a 28‐day interval, followed by twelve cycles of 375 mg/m2 rituximab maintenance therapy every 8 weeks. The primary endpoint was complete response (CR)/unconfirmed CR (CRu), at 12 weeks. Median age was 67·4 years and median FLIPI was 3. Ultimately, 18 patients (29%) had high tumour burden according to Groupe d'Etude des Lymphomes Folliculaires criteria. The 12‐week CR/CRu rate was 54·0% and the overall response rate was 93·7%. Surprisingly, 3 patients died during maintenance (2 sepsis, 1 neoplasm). Progression‐free survival was 85·4% at 24 months. In LTBFL patients with FLIPI ≥2, two cycles of rituximab and bendamustine result in a CR rate of 54·0%. However, the treatment‐related deaths observed do not allow this regimen to be recommended for LTBFL patients aged over 60 years. EudraCT: 2010‐020757‐14; ClinicalTrials.gov: NCT01313611. [ABSTRACT FROM AUTHOR]
- Published
- 2018
- Full Text
- View/download PDF
43. Event‐free survival at 24 months captures central nervous system relapse of systemic diffuse large B‐cell lymphoma in the immunochemotherapy era.
- Author
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Thanarajasingam, Gita, Maurer, Matthew J., Farooq, Umar, Johnston, Patrick B., Thompson, Carrie A., Bennani, Nabila N., Ansell, Stephen M., Porrata, Luis F., Macon, William R., Syrbu, Sergei I., Cerhan, James R., Habermann, Thomas M., Link, Brian K., Witzig, Thomas E., and Nowakowski, Grzegorz S.
- Subjects
CENTRAL nervous system ,DISEASE relapse ,B cells ,LYMPHOMAS ,RITUXIMAB - Abstract
The article focuses on the study of the central nervous system (CNS) relapse of diffuse large B-cell lymphoma (DLBCL) which is an uncommon complication of the disease. It mentions that the addition of rituximab to anthracycline-based chemotherapy immunochemotherapy (IC) has improved outcomes in patients with DLBCL.
- Published
- 2018
- Full Text
- View/download PDF
44. United we stand: Double targeting of CD79B and CD20 in diffuse large B‐cell lymphoma.
- Author
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Tarantelli, Chiara and Bertoni, Francesco
- Subjects
DIFFUSE large B-cell lymphomas ,CD20 antigen ,ANTIBODY-drug conjugates - Abstract
Summary: Polatuzumab vedotin is antibody‐drug conjugate (ADC) targeting CD79B approved for the treatment of patients with relapsed/refractory diffuse large B‐cell lymphoma when given in combination with bendamustine and rituximab. The report by Kawasaki et al. provide hints on what might be happening in lymphoma cells exposed to polatuzumab vedotin and to rituximab and on potential mechanism of resistance to the ADC. Commentary on: Kawasaki et al. The molecular rationale for the combination of polatuzumab vedotin plus rituximab in diffuse large B‐cell lymphoma. Br J Haematol 2022;199:245‐255. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
- View/download PDF
45. A tale of two antibodies: obinutuzumab versus rituximab.
- Author
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Freeman, Ciara L. and Sehn, Laurie H.
- Subjects
LYMPHOMA treatment ,CHRONIC lymphocytic leukemia treatment ,B cells ,DRUG resistance ,RITUXIMAB ,BIOSIMILARS - Abstract
Summary: While rituximab has dramatically improved outcomes for patients with CD20
+ malignancies for two decades, responses are not universal and resistance can develop. Obinutuzumab was developed to potentiate activity and overcome resistance. Pre‐clinical data suggests obinutuzumab is superior to rituximab at effecting B cell depletion; however recent phase III clinical trial results have been mixed. The decision of which antibody to employ will probably be further complicated by the approval of a subcutaneous preparation of rituximab and several anti‐CD20 biosimilars. Clinicians are now challenged with deciding whether to switch to obinutuzumab in approved settings, accepting the potential for increased toxicity and probable increased cost. The benefit conferred by obinutuzumab over rituximab may be context‐specific and vary based on histological subtype and immune integrity. This comprehensive review will explore the preclinical differences, investigate the proposed pathogenesis of rituximab resistance, compare the employed dosing strategies and interrogate available clinical results to help inform practice. [ABSTRACT FROM AUTHOR]- Published
- 2018
- Full Text
- View/download PDF
46. Inhibition of CHK1 and WEE1 as a new therapeutic approach in diffuse large B cell lymphomas with MYC deregulation.
- Author
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Restelli, Valentina, Vagni, Micaela, Arribas, Alberto J., Bertoni, Francesco, Damia, Giovanna, and Carrassa, Laura
- Subjects
LYMPHOMA treatment ,RITUXIMAB ,CHEMOTHERAPY complications - Published
- 2018
- Full Text
- View/download PDF
47. New insights in Type I and II CD20 antibody mechanismsof- action with a panel of novel CD20 antibodies.
- Author
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Meyer, Saskia, Evers, Mitchell, Jansen, Johannes H. M., Buijs, Jos, Broek, Blanca, Reitsma, Stephanie E., Moerer, Petra, Amini, Mojtaba, Kretschmer, Anna, Broeke, Toine ten, den Hartog, Marcel T., Rijke, Mark, Klein, Christian, Valerius, Thomas, Boross, Peter, and Leusen, Jeanette H. W.
- Subjects
MONOCLONAL antibodies ,CELL-mediated cytotoxicity ,CELL death ,PEPTIDES ,RITUXIMAB ,AMINO acids - Abstract
Based on their mechanisms-of-action, CD20 monoclonal antibodies (mAbs) are grouped into Type I [complement-dependent cytotoxicity (CDC) and antibody-dependent cell-mediated cytotoxicity (ADCC)] and Type II [programmed cell death (PCD) and ADCC] mAbs. We generated 17 new hybridomas producing CD20 mAbs of different isotypes and determined unique heavy and light chain sequence pairs for 13 of them. We studied their epitope binding, binding kinetics and structural properties and investigated their predictive value for effector functions, i.e. PCD, CDC and ADCC. Peptide mapping and CD20 mutant screens revealed that 10 out of these 11 new mAbs have an overlapping epitope with the prototypic Type I mAb rituximab, albeit that distinct amino acids of the CD20 molecule contributed differently. Binding kinetics did not correlate with the striking differences in CDC activity among the mIgG2c mAbs. Interestingly, chimerization of mAb m1 resulted in a mAb displaying both Type I and II characteristics. PCD induction was lost upon introduction of a mutation in the framework of the heavy chain affecting the elbow angle, supporting that structural changes within this region can affect functional activities of CD20 mAbs. Together, these new CD20 mAbs provide further insights in the properties dictating the functional efficacy of CD20 mAbs. [ABSTRACT FROM AUTHOR]
- Published
- 2018
- Full Text
- View/download PDF
48. Bendamustine, bortezomib and rituximab produces durable complete remissions in patients with previously untreated, low grade lymphoma.
- Author
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Flinn, Ian W., Thompson, Dana S., Boccia, Ralph V., Miletello, Gerald, Lipman, Andrew, Flora, Douglas, Cuevas, Daniel, Papish, Steven W., and Berdeja, Jesus G.
- Subjects
CLINICAL trials ,DRUG efficacy ,LYMPHOMA treatment ,BORTEZOMIB ,RITUXIMAB - Abstract
Abstract: This Phase II trial evaluated the efficacy of bendamustine, bortezomib and rituximab in patients with previously untreated low‐grade lymphoma. Eligible patients had low grade lymphoma with no previous systemic disease treatment. Treatment for all patients was given in 28‐day cycles for a maximum of 6 cycles. Patients received rituximab 375 mg/m
2 intravenously (IV) on days 1, 8 and 15 of cycle 1 and day 1 of cycles 2–6; bendamustine 90 mg/m2 IV on days 1 and 2; and bortezomib 1·6 mg/m2 IV on days 1, 8 and 15. Patients were permitted to begin maintenance treatment with rituximab 6 months after completion of study treatment and after 6‐month follow‐up assessments had been conducted. Fifty‐four eligible patients were enrolled. The most common grade 3/4 toxicities were leucopenia (28%), neutropenia (30%) and lymphopenia (17%). There were no treatment‐related deaths and 1 unrelated death on study (embolic stroke). The overall response rate was 94% for all patients. The median follow‐up was 54 months. Kaplan–Meier estimates of progression‐free survival and overall survival at 36 months were 75% and 88%, respectively. The treatment regimen was well tolerated and produced high response rates. Further study of this regimen in patients with previously untreated lymphoma is warranted. [ABSTRACT FROM AUTHOR]- Published
- 2018
- Full Text
- View/download PDF
49. The absolute percent deviation of IGHV mutation rather than a 98% cut-off predicts survival of chronic lymphocytic leukaemia patients treated with fludarabine, cyclophosphamide and rituximab.
- Author
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Jain, Preetesh, Nogueras González, Graciela M., Kanagal‐Shamanna, Rashmi, Rozovski, Uri, Sarwari, Nawid, Tam, Constantine, Wierda, William G., Thompson, Philip A., Jain, Nitin, Luthra, Rajyalakshmi, Quesada, Andres, Sanchez‐Petitto, Gabriela, Ferrajoli, Alessandra, Burger, Jan, Kantarjian, Hagop, Cortes, Jorge, O'Brien, Susan, Keating, Michael J., and Estrov, Zeev
- Subjects
GENETIC mutation ,IMMUNOGLOBULIN heavy chains ,GERM cells ,CHRONIC lymphocytic leukemia ,FLUDARABINE ,CYCLOPHOSPHAMIDE ,RITUXIMAB ,PROGNOSIS ,THERAPEUTICS - Abstract
The degree of somatic hypermutation, determined as percent deviation of immunoglobulin heavy chain gene variable region sequence from the germline ( IGHV%), is an important prognostic factor in chronic lymphocytic leukaemia ( CLL). Currently, a cut-off of 2% deviation or 98% sequence identity to germline in IGHV sequence is routinely used to dichotomize CLL patients into mutated and unmutated groups. Because dissimilar IGHV% cut-offs of 1-5% were identified in different studies, we wondered whether no cut-off should be applied and IGHV% treated as a continuous variable. We analysed the significance of IGHV% in 203 CLL patients enrolled on the original frontline fludarabine, cyclophosphamide and rituximab ( FCR) trial with a median of 10 years follow-up. Using the Cox Proportional Hazard model, IGHV% was identified as a continuous variable that is significantly associated with progression-free ( PFS) and overall survival ( OS) ( P < 0·001). Furthermore, we validated this finding in 323 patients treated with FCR off-protocol and in the total cohort ( n = 535). Multivariate analysis revealed a continuous trend. Higher IGHV% levels were incrementally associated with favorable PFS and OS in both FCR-treated cohorts ( P < 0·001, both cohorts). Taken together, our data suggest that IGHV% is a continuous variable in CLL patients treated with FCR. [ABSTRACT FROM AUTHOR]
- Published
- 2018
- Full Text
- View/download PDF
50. Dose-Adjusted EPOCH-R and Mid-Cycle High Dose Methotrexate for Patients with Systemic Lymphoma and secondary CNS Involvement.
- Author
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Chihara, Dai, Fowler, Nathan H., Oki, Yasuhiro, Fanale, Michelle A., Fayad, Luis E., Westin, Jason R., and Hagemeister, Fredrick B.
- Subjects
LYMPHOMA treatment ,ETOPOSIDE ,PREDNISONE ,VINCRISTINE ,DOXORUBICIN ,RITUXIMAB ,METHOTREXATE ,DRUG dosage - Abstract
The article discusses the treatment of patients with systemic lymphoma who have secondary central nervous system (CNS) involvement using dose-adjusted etoposide, prednisone, vincristine/Oncovin and doxorubicin hydrochloride in combination with rituximab (EPOCH-R) and mid-cycle high dose methotrexate. Topics discussed include survival outcome, complete response (CR) achieved by all patients, and the relapse-free status of patients who did not undergo autologous stem cell transplantation (ASCT).
- Published
- 2017
- Full Text
- View/download PDF
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