Patricia de Barros Ferreira
University of São Paulo
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Advances in Hematology | 2010
Monika Conchon; Sabri Saeed Sanabani; Mariana Serpa; Mafalda Megumi Yoshinaga Novaes; Luciana Nardinelli; Patricia de Barros Ferreira; Pedro Enrique Dorliac-Llacer; Israel Bendit
Here we report the case of an 18-year-old woman with chronic myeloid leukemia (CML) who became pregnant while undergoing treatment with dasatinib. Before pregnancy, she received imatinib mesylate therapy but could not tolerate the treatment. The regimen was then changed to dasatinib at a dose of 70 mg b.i.d. While she was in hematological remission and on dasatinib therapy, she became pregnant. The unplanned pregnancy was identified after the patient had experienced four weeks of amenorrhea. Because the patient elected to continue the pregnancy to term, dasatinib was stopped immediately. Meanwhile, CML hematological relapse occurred and then she was treated with interferon-α (IFN-α) (9 million IU/day) throughout the pregnancy without a complete hematological response. She successfully gave birth to a male baby at 33 weeks by cesarean section delivery with no sequelae or malformations. Although this experience is limited to a single patient, it provides a useful contribution for counselling patients inadvertently exposed to dasatinib during pregnancy.
Acta Haematologica | 2012
Luciana Nardinelli; Sabri Saeed Sanabani; Alline Didone; Patricia de Barros Ferreira; Mariana Serpa; Mafalda Megumi Yoshinaga Novaes; Mariana Marchiani; Antonio Lancha Ruiz; Ismael Severino Lima; Dalton de Alencar Fischer Chamone; Israel Bendit
In this retrospective study we evaluated the pretherapeutic mRNA expression of the hOCT1 (human organic cation transporter 1) gene in patients with chronic-phase (CP) chronic myeloid leukemia (CML) who varied in terms of their response to imatinib (IM). hOCT1 mRNA was quantified by real-time PCR. Patients were classified as expressing either high (n = 44) or low hOCT1 mRNA (n = 44). The complete cytogenetic response rates observed at 6, 12 and 18 months were 47.7, 84.1 and 91%, respectively, in patients with high hOCT1 mRNA and 47.5, 81.8 and 86.3%, respectively, in patients with low hOCT1 transcripts. The major molecular response rates were not significantly different between patients with high and low hOCT1 mRNA after 6 months of therapy (22.7 vs. 9.1%; p = 0.07), but they were significantly different after 12 months (54.5 vs. 31.8%; p = 0.026) and 18 months (77.2 vs. 56.8%; p = 0.034). Complete molecular responses were observed in 5 patients with low and 17 patients with high hOCT1 mRNA (p = 0.003). The 5-year event-free and overall survival analyses revealed no significant differences between the groups. These data imply that knowledge of the pretherapeutic level of hOCT1 could be a useful marker to predict IM therapy outcome in treatment-naïve CP CML patients.
BMC Hematology | 2010
Mariana Serpa; Sabri Saeed Sanabani; Pedro Enrique Dorliac-Llacer; Monika Conchon; Thales Dalessandro Meneguin Pereira; Luciana Nardinelli; Juliana Lima Costa; Mafalda Megumi Yoshinaga Novaes; Patricia de Barros Ferreira; Israel Bendit
BackgroundThe monitoring of BCR-ABL transcript levels by real-time quantitative polymerase chain reaction (RT-qPCR) has become important to assess minimal residual disease (MRD) and standard of care in the treatment of chronic myeloid leukemia (CML). In this study, we performed a prospective, sequential analysis using RT-qPCR monitoring of BCR-ABL gene rearrangements in blood samples from 91 CML patients in chronic phase (CP) who achieved complete cytogenetic remission (CCyR) and major molecular remission (MMR) throughout imatinib treatment.MethodsThe absolute level of BCR-ABL transcript from peripheral blood was serially measured every 4 to 12 weeks by RT-qPCR. Only level variations > 0.5%, according to the international scale, was considered positive. Sequential cytogenetic analysis was also performed in bone marrow samples from all patients using standard protocols.ResultsBased on sequential analysis of BCR-ABL transcripts, the 91 patients were divided into three categories: (A) 57 (62.6%) had no variation on sequential analysis; (B) 30 (32.9%) had a single positive variation result obtained in a single sample; and (C) 4 (4.39%) had variations of BCR-ABL transcripts in at least two consecutive samples. Of the 34 patients who had elevated levels of transcripts (group B and C), 19 (55.8%) had a < 1% of BCR-ABL/BCR ratio, 13 (38.2%) patients had a 1% to 10% increase and 2 patients had a >10% increase of RT-qPCR. The last two patients had lost a CCyR, and none of them showed mutations in the ABL gene. Transient cytogenetic alterations in Ph-negative cells were observed in five (5.5%) patients, and none of whom lost CCyR.ConclusionsDespite an increase levels of BCR-ABL/BCR ratio variations by RT-qPCR, the majority of CML patients with MMR remained in CCyR. Thus, such single variations should neither be considered predictive of subsequent failure and nor an indication for altering imatinib dose or switching to second generation therapy. Changing of imatinib on the basis of BCR-ABL/BCR% sustained increase and mutational studies is a prudent approach for preserving other therapeutic options in imatinib-resistant patients.
Acta Haematologica | 2012
Israel Bendit; Sabri Saeed Sanabani; Monika Conchon; Mariana Serpa; Mafalda Megumi Yoshinaga Novaes; Luciana Nardinelli; Thales Dalessandro Meneguin Pereira; Luciana Tucunduva; Patricia de Barros Ferreira; Pedro Enrique Dorlhiac-Llacer; Dalton de Alencar Fischer Chamone
Here we compare the management and survival outcomes of chronic myeloid leukemia (CML) patients who had early or late imatinib mesylate (IM) therapy. The cytogenetic and molecular responses of 189 CML patients were analyzed. Of this group, 121 patients were classified as the early chronic phase (ECP) group and started IM within 12 months of diagnosis. The other 68 patients were classified as the late chronic phase (LCP) group who had been treated with interferon (IFN)-alpha-2 and crossed over to IM more than 12 months after diagnosis. The overall rates of complete cytogenetic response (CCyR) and major molecular response (MMR) at last follow-up were 83.6 and 78.1% in the ECP and LCP groups, respectively. The CCyR rates were 89.3 (for ECP patients) versus 73.5% (for LCP patients; p < 0.0001). At last follow-up, 82.4% ECP and 64.2% LCP patients had achieved an MMR (p < 0.0001). No significant differences were noted between the two groups with regard to survival outcomes. Our experience reveals that IM is an effective rescue therapy in most CML LCP patients who are intolerant or in whom IFN-alpha therapy fails. Such therapeutic options should be considered in LCP patients, particularly in countries where IM may not be available.
Revista Brasileira De Hematologia E Hemoterapia | 2011
Roberta Sandra da Silva Tanizawa; Cristina Aiko Kumeda; Raymundo Soares de Azevedo Neto; Aline M. Leal; Patricia de Barros Ferreira; Elvira Deolinda Rodrigues Pereira Velloso
Background Secondary myeloid neoplasms comprise a group of secondary diseases following exposure to myelotoxic agents or due to congenital diseases. The improvement of anticancer agents and immunosuppressive drugs seem to be associated with an increased incidence of secondary myeloid neoplasms. Karyotyping of bone marrow is essential for diagnosis and prognosis. Previous use of alkylating agents and radiation are associated with clonal abnormalities such as recurrent unbalanced -5/5q-, -7/7q- and complex karyotypes, whereas topoisomerase-II inhibitors lead to changes such as the balanced 11q23 rearrangement, t(8;21), t(15;17) and inv(16). Objective To study the clinical and cytogenetic data of patients with secondary myeloid neoplasms who took antineoplastic and/or immunosuppressive drugs or progressed from aplastic anemia. Methods The clinical and cytogenetic characteristics of 42 patients diagnosed with secondary myeloid neoplasms in one institution were retrospectively evaluated. Of these, 25, 11 and 6 patients had had oncological diseases, aplastic anemia and other diseases, respectively. Conventional cytogenetic and FISH analyses were performed for monosomy 7. Results The cytogenetic study was conclusive in 32 cases with 84.4% of clonal abnormalities. Monosomy 7 and complex karyotypes were present in 44.4% and 37%, respectively. A high prevalence of unbalanced abnormalities (96.3%) was observed. Monosomy 7 was more prevalent in patients with myelodysplastic syndromes/myeloid neoplasms after aplastic anemia (66.6%). The median survival after diagnosis of myeloid neoplasms was only 5.7 months. Normal cytogenetics was associated to better survival (p-value = 0.03). There was a slightly worse trend of survival for patients with complex karyotypes (p-value = 0.057). Abnormal karyotype was an independent risk factor for poor survival (p-value = 0.012). Conclusion This study enhances the importance of cytogenetic analysis of patients at the time of diagnosis of secondary myeloid neoplasms.
Leukemia Research | 2013
M. Silva; A. Leal; Patricia de Barros Ferreira; L. Nardinelly; L. Pelicario; T. Lopes; I. Bendit; Elvira Deolinda Rodrigues Pereira Velloso
Introduction: Myelodysplastic syndromes (MDS) are a group of heterogenous clonal stem cell disorders characterized by inefficient haematopoiesis with one or more cytopenias and increased risk of transformation to acute leukemia. Purpose: The current diagnosis includes peripheral blood morphology, bone marrow biopsy and cytogenetic exam. Clonal cytogenetic abnormalities are described in 40-60% of cases. In 1997, the established System of International Prognostic Score was based on the number of cytopenias on the peripheral blood, precentage bone marrow blasts and karyotype abnomalities. In this system are described a limited number of cytogenetic abnormalities and the importance of their forecast is underestimated. This score classify patients into four risk groups, allow overall survival and estimate the risk of progression to acute leukemia. Materials and Methods: In September 2012 the Revised International Prognostic Scoring System (R-IPSS) was developed in the framework of a project of the International Working Group for Prognosis in MDS (IWG-PM) peak. For scoring according to IPSS-R, it was taken into account: severity of cytopenias (Hb level, the number of platelets, the absolute number of neutrophils), the percentage of bone marrow blasts and cytogenetic exam. It was found that this system prognostic allows a better classification of patients with MDS into risk groups. We analyzed 25 patients diagnosed with MDS, according to theWHO classification 2001, with low risk and intermediate-1 during the period 2008-2012. These patients have been hospitalized in three centers of Hematology Departments from Romania. Results: The lot of patients was evaluated according to R-IPSS (2012) and it was found that the new system allows a better prognosis estimation and more accurate patient risk group classification. Conclusions: Although according to IPSS (1997), all patients included in this studywere low risk (0-1) but applying the new scoring system has allowed a better classification of patients, six of them were with intermediate and high risk (3,5-6).
Acta Haematologica | 2012
Sabri Saeed Sanabani; Monika Conchon; Mariana Serpa; Mafalda Megumi Yoshinaga Novaes; Luciana Nardinelli; Thales Dalessandro Meneguin Pereira; Luciana Tucunduva; Patricia de Barros Ferreira; Pedro Enrique Dorlhiac-Llacer; Dalton de Alencar Fischer Chamone; Israel Bendit; Hiromichi Matsushita; Makoto Onizuka; Naoya Nakamura; Jun Amaki; Yasuyuki Aoyama; Hidetsugu Kawai; Yoshiaki Ogawa; Hiroshi Kawada; Kiyoshi Ando; Daisuke Ohgiya; Suleimman A. Al-Sweedan; Nor Awwad; Milos Kuzmanovic; Natasa Tosic; Natasa Colovic; Teodora Karan-Djurasevic; Vesna Spasovski; Milena Radmilovic; Gordana Nikcevic
Gregory A. Abel, Boston, USA Athanasios Aessopos, Athens, Greece Xabier Agirre, Navarra, Spain Graciela S. Alarcon, Birmingham, USA J.P. Allain, Cambridge, UK S.D. Anker, Berlin, Germany Jane F. Apperley, London, UK A. Arai, Tokyo, Japan Aderson Araújo, Recife, Brazil Luca Arcaini, Pavia, Italy Paolo Arese, Torino, Italy Maurizio Aricò, Florence, Italy Scott A. Armstrong, Boston, USA Roopen Arya, London, UK Giuseppe Avvisati, Rome, Italy Yesim Aydinok, Izmir, Turkey Ulrike Bacher, Hamburg, Germany Andrea Bacigalupo, Genoa, Italy Catherine Bagot, Glasgow, UK Carmen Baldazzi, Bologna, Italy Bernadett Balla, Budapest, Hungary David Barnett, Sheffield, UK Giovanni Barosi, Pavia, Italy Sharon L. Barrans, Leeds, UK Eva Bartova, Brno, Czech Republic Christian Bastard, Rouen, France Heiko Becker, Freiburg, Germany John M. Bennett, Rochester, USA M. Bennett, Afula, Israel J.A. Bernstein, Cincinnati, USA Erik Berntorp, Malmo, Sweden Alain Berrebi, Rehovot, Israel Caroline Besson, Le Kremlin-Bicêtre, France Wolfgang A. Bethge, Tübingen, Germany Deepa Bhojwani, Memphis, USA Janet J. Bijl, Montréal, Canada Douglas P. Blackall, Little Rock, USA Olga Blau, Berlin, Germany Dominique Bonnefont-Rousselot, Paris, France X. Bosch, Barcelona, Spain Reda Bouabdallah, Marseille, France Vassiliki A. Boussiotis, Boston, USA From September 1, 2011 to August 31, 2012 a number of additional referees assisted the editors with reviews of the submitted papers. The editors would like to thank the following colleagues:
Acta Haematologica | 2012
Mariana Serpa; Sabri Saeed Sanabani; Pedro Enrique Dorlhiac-Llacer; Luciana Nardinelli; Patricia de Barros Ferreira; Thays Fernanda Borges Martins; Fernanda Seguro; Israel Bendit
Despite the beneficial effects of imatinib mesylate, some patients may either not respond or respond suboptimally. Here, we report two chronic myelogenous leukemia patients; one had a suboptimal response according to European LeukemiaNet criteria (a major molecular response was not achieved after 18 months of standard-dose imatinib therapy) and the other had failure with a standard dose of imatinib. At the time of the suboptimal response in patient 1 and the failure in patient 2, we were able to detect the F359I mutation in the BCR-ABL tyrosine kinase domain using DNA sequencing in both patients. Therefore, it was decided to change the therapeutic regimen to dasatinib at a dose of 100 mg once daily in both patients. This change resulted in the achievement of complete cytogenetic remission in patient 1 after 4 months and a major molecular response within 2 and 3 months in both patients. Detection of the F359I mutation in our two cases likely explains the suboptimal response to imatinib in case 1 and the failure in case 2. This implies that in such cases dasatinib should be considered to effectively suppress the mutated clones.
Leukemia Research | 2013
Márcio Luís Andrade e Silva; R.S. Azevedo Neto; Aline M. Leal; Patricia de Barros Ferreira; Cristina Aiko Kumeda; Roberta Sandra da Silva Tanizawa; A. Mascarenhas; W. Lima; V. Buccheri; Elvira Deolinda Rodrigues Pereira Velloso
Acta Haematologica | 2012
Sabri Saeed Sanabani; Monika Conchon; Mariana Serpa; Mafalda Megumi Yoshinaga Novaes; Luciana Nardinelli; Thales Dalessandro Meneguin Pereira; Luciana Tucunduva; Patricia de Barros Ferreira; Pedro Enrique Dorlhiac-Llacer; Dalton de Alencar Fischer Chamone; Israel Bendit; Hiromichi Matsushita; Makoto Onizuka; Naoya Nakamura; Jun Amaki; Yasuyuki Aoyama; Hidetsugu Kawai; Yoshiaki Ogawa; Hiroshi Kawada; Kiyoshi Ando; Daisuke Ohgiya; Suleimman A. Al-Sweedan; Nor Awwad; Milos Kuzmanovic; Natasa Tosic; Natasa Colovic; Teodora Karan-Djurasevic; Vesna Spasovski; Milena Radmilovic; Gordana Nikcevic