JULIANA PEREIRA
Projetos de Pesquisa
Unidades Organizacionais
Departamento de Clínica Médica, Faculdade de Medicina - Docente
LIM/31 - Laboratório de Genética e Hematologia Molecular, Hospital das Clínicas, Faculdade de Medicina - Líder
LIM/31 - Laboratório de Genética e Hematologia Molecular, Hospital das Clínicas, Faculdade de Medicina - Líder
8 resultados
Resultados de Busca
Agora exibindo 1 - 8 de 8
- Epstein-Barr Viral Load is Associated to Response in AIDS-Related Lymphomas(2014) TANAKA, Paula Yurie; OHSHIMA, Kouichi; MATSUOKA, Masao; SABINO, Ester Cerdeira; FERREIRA, Suzete Cleusa; NISHYA, Anna Shoko; COSTA, Renata de Oliveira; CALORE, Edenilson Eduardo; PEREZ, Nilda Maria; PEREIRA, JulianaAIDS-related lymphoma (ARL) development is associated to immunodeficiency state with proliferation of B-cells driven by HIV itself and EBV infection. However, Epstein-Barr DNA is not detected in malignant cells of all ARL subtypes. A prospective and controlled study to analyze EBV viral load (VL) in plasma and peripheral blood mononuclear cells (PBMC) of ARL patients was performed to analyze if Epstein-Barr VL could be related to response in these patients. Fifteen patients with ARL were included in this study with measurement of EBV VL at three different periods of time: at lymphoma diagnosis, upon completion of chemotherapy, and 3 months after. Two control groups composed by HIV-negative and HIV-positive patients were also evaluated for EBV VL comparison. In situ hybridization for EBER was performed on diagnostic samples of all ARL patients. Median EBV VL in PBMC and plasma had a significant decrease (p = 0.022 and p = 0.003, respectively) after ARL treatment. EBER was positive in 7 (46.7 %) cases. Median EBV VL in PBMC before lymphoma treatment in patients positive for EBER was significantly higher compared to EBER negative cases (p = 0.041). Reduction of EBV viral load during treatment of lymphoma could be predictive of response. EBER expression was associated to advanced stages of disease and worse immune status. Our study suggests that measurement of EBV VL during ARL treatment could be used as a marker for response, but further studies are needed to validate this association.
- Association between bortezomib dose intensity and overall survival in mantle cell lymphoma patients on frontline VR-CAP in the phase 3 LYM-3002 study(*)(2019) ROBAK, Tadeusz; HUANG, Huiqiang; JIN, Jie; ZHU, Jun; LIU, Ting; SAMOILOVA, Olga; PYLYPENKO, Halyna; VERHOEF, Gregor; SIRITANARATKUL, Noppadol; OSMANOV, Evgenii; PEREIRA, Juliana; MAYER, Jiri; HONG, Xiaonan; OKAMOTO, Rumiko; PEI, Lixia; ROONEY, Brendan; VELDE, Helgi van de; CAVALLI, FrancoThe pivotal LYM-3002 study compared frontline rituximab plus cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP) with bortezomib, rituximab, cyclophosphamide, doxorubicin and prednisone (VR-CAP) in newly diagnosed mantle cell lymphoma (MCL) patients for whom stem cell transplantation was not an option. This post hoc subanalysis of the VR-CAP data from LYM-3002 evaluated the effect of bortezomib dose intensity on OS in patients who completed >= 6 cycles of treatment. From the end of cycle 6, patients receiving >= 4.6 mg/m(2)/cycle of bortezomib had significantly longer OS (but not PFS) compared with those receiving <4.6 mg/m(2)/cycle by univariate analysis (HR 0.43 [95% CI: 0.23-0.80]; p = .0059). This association remained significant in multivariate analysis adjusting for baseline patient and disease characteristics (HR 0.40 [95% CI: 0.20-0.79]; p = .008]. Higher bortezomib dose intensity was the strongest predictor of OS in newly diagnosed MCL patients receiving VR-CAP. Clinicaltrials.gov identifier: NCT00722137.
- Bortezomib-Based Therapy for Newly Diagnosed Mantle-Cell Lymphoma(2015) ROBAK, Tadeusz; HUANG, Huiqiang; JIN, Jie; ZHU, Jun; LIU, Ting; SAMOILOVA, Olga; PYLYPENKO, Halyna; VERHOEF, Gregor; SIRITANARATKUL, Noppadol; OSMANOV, Evgenii; ALEXEEVA, Julia; PEREIRA, Juliana; DRACH, Johannes; MAYER, Jiri; HONG, Xiaonan; OKAMOTO, Rumiko; PEI, Lixia; ROONEY, Brendan; VELDE, Helgi van de; CAVALLI, FrancoBACKGROUND The proteasome inhibitor bortezomib was initially approved for the treatment of relapsed mantle-cell lymphoma. We investigated whether substituting bortezomib for vincristine in frontline therapy with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) could improve outcomes in patients with newly diagnosed mantle-cell lymphoma. METHODS In this phase 3 trial, we randomly assigned 487 adults with newly diagnosed mantle-cell lymphoma who were ineligible or not considered for stem-cell transplantation to receive six to eight 21-day cycles of R-CHOP intravenously on day 1 (with prednisone administered orally on days 1 to 5) or VR-CAP (R-CHOP regimen, but replacing vincristine with bortezomib at a dose of 1.3 mg per square meter of body-surface area on days 1, 4, 8, and 11). The primary end point was progression-free survival. RESULTS After a median follow-up of 40 months, median progression-free survival (according to independent radiologic review) was 14.4 months in the R-CHOP group versus 24.7 months in the VR-CAP group (hazard ratio favoring the VR-CAP group, 0.63; P<0.001), a relative improvement of 59%. On the basis of investigator assessment, the median durations of progression-free survival were 16.1 months and 30.7 months, respectively (hazard ratio, 0.51; P<0.001), a relative improvement of 96%. Secondary end points were consistently improved in the VR-CAP group, including the complete response rate (42% vs. 53%), the median duration of complete response (18.0 months vs. 42.1 months), the median treatment-free interval (20.5 months vs. 40.6 months), and the 4-year overall survival rate (54% vs. 64%). Rates of neutropenia and thrombocytopenia were higher in the VR-CAP group. CONCLUSIONS VR-CAP was more effective than R-CHOP in patients with newly diagnosed mantle-cell lymphoma but at the cost of increased hematologic toxicity. (Funded by Janssen Research and Development and Millennium Pharmaceuticals; LYM-3002 ClinicalTrials.gov number, NCT00722137.)
conferenceObject Final overall survival results of frontline bortezomib plus rituximab, cyclophosphamide, doxorubicin, and prednisone (VR-CAP) vs R-CHOP in transplantation-ineligible patients (pts) with newly diagnosed mantle-cell lymphoma (MCL): A randomized, open-label, phase III (LYM-3002) study(2018) CAVALLI, F.; JIN, J.; PYLYPENKO, H.; VERHOEF, G.; SIRITANARATKUL, N.; DRACH, J.; RADERER, M.; MAYER, J.; PEREIRA, J.; TUMYAN, G.; OKAMOTO, R.; NAKAHARA, S.; HU, P.; APPIANI, C.; NEMAT, S.; ROBAK, T.conferenceObject Bortezomib (Btz) Dose Intensity Is the Strongest Predictor for Overall Survival (OS) in Mantle Cell Lymphoma (MCL) Patients (Pts) Not Considered for Transplantation, Receiving Frontline Btz Plus Rituximab, Cyclophosphamide, Doxorubicin, and Prednisone (VR-CAP) Therapy in the Phase 3 LYM-3002 Study(2014) ROBAK, Tadeusz; HUANG, Huiqiang; JIN, Jie; ZHU, Jun; LIU, Ting; SAMOILOVA, Olga S.; PYLYPENKO, Halyna; VERHOEF, Gregor; SIRITANARATKUL, Noppadol; OSMANOV, Evgenii A.; ALEXEEVA, Julia; PEREIRA, Juliana; MAYER, Jiri; HONG, Xiaonan; MAEDA, Yoshiharu; PEI, Lixia; ROONEY, Brendan; VELDE, Helgi van de; CAVALLI, Franco- GATA-3 is a proto-oncogene in T-cell lymphoproliferative neoplasms(2022) GENG, Xiangrong; WANG, Chenguang; GAO, Xin; CHOWDHURY, Pinki; WEISS, Jonathan; VILLEGAS, Jose A.; SAED, Badeia; PERERA, Thilini; HU, Ying; RENEAU, John; SVERDLOV, Maria; WOLFE, Ashley; BROWN, Noah; HARMS, Paul; BAILEY, Nathanael G.; INAMDAR, Kedar; HRISTOV, Alexandra C.; TEJASVI, Trilokraj; MONTES, Jaime; BARRIONUEVO, Carlos; TAXA, Luis; CASAVILCA, Sandro; LAGE, J. Luis Alberto de Padua Covas; CULLER, Hebert Fabricio; PEREIRA, Juliana; RUNGE, John S.; QIN, Tingting; TSOI, Lam C.; HONG, Hanna S.; ZHANG, Li; LYSSIOTIS, Costas A.; OHE, Rintaro; TOUBAI, Tomomi; ZEVALLOS-MORALES, Alejandro; MURGA-ZAMALLOA, Carlos; WILCOX, Ryan A.Neoplasms originating from thymic T-cell progenitors and post-thymic mature T-cell subsets account for a minority of lymphoproliferative neoplasms. These T-cell derived neoplasms, while molecularly and genetically heterogeneous, exploit transcription factors and signaling pathways that are critically important in normal T-cell biology, including those implicated in antigen-, costimulatory-, and cytokine-receptor signaling. The transcription factor GATA-3 regulates the growth and proliferation of both immature and mature T cells and has recently been implicated in T-cell neoplasms, including the most common mature T-cell lymphoma observed in much of the Western world. Here we show that GATA-3 is a proto-oncogene across the spectrum of T-cell neoplasms, including those derived from T-cell progenitors and their mature progeny, and further define the transcriptional programs that are GATA-3 dependent, which include therapeutically targetable gene products. The discovery that p300-dependent acetylation regulates GATA-3 mediated transcription by attenuating DNA binding has novel therapeutic implications. As most patients afflicted with GATA-3 driven T-cell neoplasms will succumb to their disease within a few years of diagnosis, these findings suggest opportunities to improve outcomes for these patients.
- Association between quality of response and outcomes in patients with newly diagnosed mantle cell lymphoma receiving VR-CAP versus R-CHOP in the phase 3 LYM-3002 study(2017) VERHOEF, Gregor; ROBAK, Tadeusz; HUANG, Huiqiang; PYLYPENKO, Halyna; SIRITANARATKUL, Noppadol; PEREIRA, Juliana; DRACH, Johannes; MAYER, Jiri; OKAMOTO, Rumiko; PEI, Lixia; ROONEY, Brendan; CAKANA, Andrew; VELDE, Helgi van de; CAVALLI, FrancoIn the phase 3 LYM-3002 study comparing intravenous VR-CAP with R-CHOP in patients with newly-diagnosed, measurable stage II-IV mantle cell lymphoma, not considered or ineligible for transplant, the median progression-free survival was significantly improved with VR-CAP (24.7 versus 14.4 months with R-CHOP; P<0.001). This post-hoc analysis evaluated the association between the improved outcomes and quality of responses achieved with VR-CAP versus R-CHOP in LYM-3002. Patients were randomized to six to eight 21-day cycles of VR-CAP or R-CHOP. Outcomes included progression-free survival, duration of response (both assessed by an independent review committee), and time to next anti-lymphoma treatment, evaluated by response (complete response/unconfirmed complete response and partial response), MIPI risk status, and maximum reduction of lymph-node measurements expressed as the sum of the product of the diameters. Within each response category, the median progression-free survival was longer for patients given VR-CAP than for those given R-CHOP (complete response/unconfirmed complete response: 40.9 versus 19.8 months; partial response: 17.1 versus 11.7 months, respectively); similarly, the median time to next anti-lymphoma treatment was longer among the patients given VR-CAP than among those treated with R-CHOP (complete response/unconfirmed complete response: not evaluable versus 26.6 months; partial response: 35.3 versus 24.3 months). Within the complete/unconfirmed complete and partial response categories, improvements in progression-free survival, duration of response and time to next anti-lymphoma treatment were more pronounced in patients with low- and intermediate-risk MIPI treated with VR-CAP than with R-CHOP. In each response category, more VR-CAP than R-CHOP patients had a sum of the product of the diameters nadir of 0 during serial radiological assessments. Results of this post-hoc analysis suggest a greater duration and quality of response in patients treated with VR-CAP in comparison with those treated with R-CHOP, with the improvements being more evident in patients with low-and intermediate-risk MIPI. LYM-3002 ClinicalTrials.gov: NCT00722137.
- Frontline bortezomib, rituximab, cyclophosphamide, doxorubicin, and prednisone (VR-CAP) versus rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) in transplantation-ineligible patients with newly diagnosed mantle cell lymphoma: final overall survival results of a randomised, open-label, phase 3 study(2018) ROBAK, Tadeusz; JIN, Jie; PYLYPENKO, Halyna; VERHOEF, Gregor; SIRITANARATKUL, Noppadol; DRACH, Johannes; RADERER, Markus; MAYER, Jiri; PEREIRA, Juliana; TUMYAN, Gayane; OKAMOTO, Rumiko; NAKAHARA, Susumu; HU, Peter; APPIANI, Carlos; NEMAT, Sepideh; CAVALLI, FrancoBackground In the LYM-3002 study, the efficacy and safety of frontline bortezomib plus rituximab, cyclophosphamide, doxorubicin, and prednisone (VR-CAP) and rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) were compared in transplant-ineligible patients with untreated, newly diagnosed, mantle cell lymphoma. We report the final overall survival and safety outcomes for patients in the long-term follow-up phase after the primary progression-free-survival endpoint was met. Methods LYM-3002 was a randomised, open-label, phase 3 study done at 128 clinical centres in 28 countries in Asia, Europe, North America, and South America. Adult patients with confirmed stage II-IV previously untreated mantle cell lymphoma, Eastern Cooperative Oncology Group performance status score of 2 or less, who were ineligible for bone marrow transplantation, were randomly assigned (1: 1) to receive six or eight 21-day cycles of VR-CAP (intravenous rituximab 375 mg/m(2), cyclophosphamide 750 mg/m(2), doxorubicin 50 mg/m(2), and bortezomib 1.3 mg/m(2), plus oral prednisone 100 mg/m(2)) or R-CHOP (intravenous vincristine 1.4 mg/m(2) [2 mg maximum], rituximab 375 mg/m(2), cyclophosphamide 750 mg/m(2), and doxorubicin 50 mg/m(2), plus oral prednisone 100 mg/m(2)). Randomisation was done according to a computer-generated randomisation schedule prepared by the sponsor; permuted blocks central randomisation was used (block size of 4), and was stratified by International Prognostic Index score and disease stage at diagnosis. The primary endpoint of this final analysis was overall survival, which was analysed in the intention-totreat population. This study is registered with ClinicalTrials.gov, number NCT00722137, and is closed to new participants with follow-up completed. Findings Between May 22, 2008, and Dec 5, 2011, 487 patients were enrolled and randomly assigned. 268 patients (140 in the VR-CAP group and 128 in the R-CHOP group) were included in the follow-up analysis, which included patients with data available after the primary analysis clinical cutoff date of Dec 2, 2013. After median follow-up of 82.0 months (IQR 74.1-94.2), median overall survival was significantly longer in the VR-CAP group than in the R-CHOP group (90.7 months [95% CI 71.4 to not estimable] vs 55.7 months [47.2 to 68.9]; hazard ratio 0.66 [95% CI 0.51-0.85]; p=0.001). Three new adverse events were reported since the primary analysis cutoff (one each of grade 4 lung adenocarcinoma and grade 4 gastric cancer in the VR-CAP group, and one case of grade 2 pneumonia in the R-CHOP group). 103 (42%) of 243 patients in the VR-CAP group, and 138 (57%) of 244 in the R-CHOP group died; the most common cause of death was progressive disease. Interpretations Compared with R-CHOP, VR-CAP was associated with significantly longer survival, and had a manageable and expected safety profile. Our results support further assessment of VR-CAP in patients with previously untreated mantle cell lymphoma.