22 results on '"Katia B Pagnano"'
Search Results
2. Evaluation of anemia after long-term treatment with imatinib in chronic myeloid leukemia patients in chronic phase
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Thais Celi Lopes Benevides, Gislaine Oliveira Duarte, Irene Lorand-Metze, Roberto Zulli, Marcia Torresan Delamain, Carmino Antonio De Souza, Priscila de Oliveira Percout, Maria Almeida Dias, Katia B Pagnano, and Muriel Silva Moura
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medicine.medical_specialty ,Anemia ,Population ,Gastroenterology ,Internal medicine ,hemic and lymphatic diseases ,medicine ,Immunology and Allergy ,Vitamin B12 ,education ,Adverse effect ,neoplasms ,education.field_of_study ,business.industry ,lcsh:RC633-647.5 ,Incidence (epidemiology) ,Chronic myeloid leukemia ,Myeloid leukemia ,Imatinib ,Hematology ,Iron deficiency ,lcsh:Diseases of the blood and blood-forming organs ,medicine.disease ,Adverse events ,Original Article ,business ,medicine.drug - Abstract
Introduction: The incidence of grade 3–4 anemia was reported to be 3% with imatinib therapy for newly diagnosed chronic myeloid leukemia (CML) in the chronic phase (CP). However, there are few data regarding the causes and the development of anemia after long-term treatment. This study aimed to evaluate the incidence of anemia after at least two years of imatinib treatment of CML patients in the CP and to identify other contributing causes of anemia in this population. Patients and methods: We performed a retrospective analysis of 97 CML patients in the CP treated with imatinib for at least two years. We analyzed the hemoglobin (Hb) levels of CML patients at diagnosis, upon initiation of treatment with imatinib and after two years of imatinib treatment, and investigated other causes of anemia in this population. Results: Most of the patients presented Hb levels below the normal range (80.4%) after the second year of treatment, 17.9% grade 2 and 1.3% grade 3. In 13 cases (16.7%), anemia was attributed to resistance and in 13 cases (16.7%) the following causes were identified: iron deficiency (n = 5), hypothyroidism (n = 2), vitamin B12 deficiency (n = 3), acquired immune deficiency syndrome (AIDS) (n = 1), pulmonary tuberculosis (n = 1) and renal toxicity (n = 1). In 52 patients (66.6%), there were no other factors contributing to anemia, except imatinib treatment. Conclusion: Regular follow-up is required to identify the causes of anemia not related to CML or imatinib toxicity. The importance of investigating secondary causes of anemia should be emphasized, especially in patients with good adherence to treatment and satisfactory therapeutic response. Keywords: Chronic myeloid leukemia, Imatinib, Anemia, Adverse events
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- 2019
3. Guideline on myeloproliferative neoplasms: Associacão Brasileira de Hematologia, Hemoterapia e Terapia Cellular
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Israel Bendit, Maria de Lourdes Lopes Ferrari Chauffaille, Laura Fogliatto, Renato Tavares, Nelma Cristina D. Clementino, Alexandre Nonino, Wanderley Marques Bernardo, Monika Conchon, Fabio P. Santos, Vaneuza Araujo Moreira Funke, Ana Clara Kneese Virgilio do Nascimento, and Katia B Pagnano
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Thrombopoietin receptor ,Chronic eosinophilic leukemia ,Essential thrombocythemia ,business.industry ,Chronic neutrophilic leukemia ,Myeloid leukemia ,Hematology ,medicine.disease ,Philadelphia chromosome ,Article ,Polycythemia vera ,hemic and lymphatic diseases ,medicine ,Cancer research ,Immunology and Allergy ,Myelofibrosis ,business - Abstract
Myeloproliferative neoplasms (MPNs) constitute a group of hematologic clonal diseases that affect one or more myeloid lineages with an abnormal and abundant proliferation.16, 17 The World Health Organization (WHO) currently groups the MPNs into seven categories: Chronic myeloid leukemia (CML), chronic neutrophilic leukemia (CNL), polycythemia vera (PV), essential thrombocythemia (ET) primary myelofibrosis (PMF), chronic eosinophilic leukemia not otherwise specified (NOS) and, unclassifiable chronic myeloproliferative neoplasm (MPN-U). Mastocytosis is no longer included in that group.16 BCR-ABL1 fusion gene causes CML, identified by the translocation (9; 22) known as the Philadelphia chromosome (Ph), subject of prior guideline. Among the so-called Ph-negative MPNs, the most common ones include PV, ET, and PMF, herein the subject of this publication. PV, ET, and PMF share an anomaly in the JAK-STAT pathway, usually caused by genetic mutations on Janus kinase 2-JAK2 V617F, thrombopoietin receptor gene-myeloproliferative leukemia-MPL or calreticulin gene-CALR, which are mutually exclusive, and necessarily BCR-ABL negative (Table 1). PV, ET, and PMF share an anomaly in the JAK-STAT pathway, usually caused by mutations of the Janus kinase 2-JAK2 V617F genes, thrombopoietin receptor gene-myeloproliferative leukemia-MPL or calreticulin gene-CALR, that are mutually exclusive, and necessarily are BCR-ABL1 negative (Table 1). PV, ET, and PMF may arise alongside other mutations, as well as some cytogenetic abnormalities.16, 17 Despite the significant advances over recent years toward the characterization of genetic alterations, bone marrow morphological evaluation remains an important diagnosis tool.17 JAK2, MPL, and CALR mutations are not unique to these three conditions and may be present in other myeloid neoplasms, or even absent in some cases of PMF and ET.16 Table 1 Diagnostic criteria PV, ET, prefibrotic PMF and overt fibrotic PMF16(D).
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- 2019
4. Management of chronic myeloid leukemia during pregnancy: a retrospective analysis at a single center
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Ariella Cássia de Moura, Katia B Pagnano, Gislaine Oliveira Duarte, Marcia Torresan Delamain, Irene Lorand-Metze, and Carmino Antonio De Souza
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Pediatrics ,medicine.medical_specialty ,Dasatinib ,030204 cardiovascular system & hematology ,Single Center ,03 medical and health sciences ,0302 clinical medicine ,Pregnancy ,hemic and lymphatic diseases ,medicine ,Immunology and Allergy ,Hydroxyurea ,Adverse effect ,business.industry ,lcsh:RC633-647.5 ,Chronic myeloid leukemia ,Myeloid leukemia ,Interferon-alpha ,Imatinib ,Hematology ,Leukapheresis ,lcsh:Diseases of the blood and blood-forming organs ,medicine.disease ,Gestation ,Original Article ,business ,030215 immunology ,medicine.drug - Abstract
We analyzed the management and outcomes of pregnancies of patients with chronic myeloid leukemia at a single center over fifteen years. Among the 203 CML female patients, there were ten pregnancies in seven women, all of them not planned. In three cases, the chronic myeloid leukemia diagnosis was made during pregnancy. Five patients received tyrosine kinase inhibitors in the first weeks of pregnancy and the drug was interrupted until delivery. One patient lost complete cytogenetic response, and two patients lost the hematological response. A patient with a stable major molecular response had two successful pregnancies without loss of response. There were four premature births. There were no maternal adverse events, fetal malformation or death. All patients received Interferon-alpha during gestation, and two received hydroxyurea for a short period. Leukapheresis was performed in two patients for hyperleukocytosis control. One patient with sickle cell disease died from disease progression six months after delivery. Conclusions: The tyrosine kinase inhibitors ministration should be interrupted during pregnancy. Patients should be advised to achieve a stable and deep molecular response if they plan to conceive, to avoid the risk of disease progression. Keywords: Chronic myeloid leukemia, Pregnancy, Imatinib, Interferon-alpha, Hydroxyurea, Dasatinib
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- 2019
5. COVID-19 in chronic myeloid leukemia patients in Latin America
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Katia B Pagnano, Jaqueline Sapelli, Leila Martins Perobelli, LC Palma, Jaisson Bortolini, Leonardo Fechio, Roberto Zulli, Beatriz Moiraghi, Ana Carolina Mourão Toreli, Luciene Da Cruz Oliveira, Acy Telles de Souza Quixadá, Evelyn Herrera Peralta, André L G Lourenço, Vaneuza Araujo Moreira Funke, Juan Ramon Navarro, Muriel Silva Moura, Monika Conchon, Carolina Pavlovsky, Nancy Delgado, Natália N Gonçalves, Fernanda S Seguro, Israel Bendit, Fabio Moore Nucci, Lilian Pilleux, Leandro Lustri Almeida, Carmino Antonio De Souza, Lourdes Del Rosario David Salas, Paula de Oliveira Montandon Hokama, Carla Boquimpani, Universidade Estadual de Campinas (UNICAMP), Hospital Nacional Edgardo Rebagliati Martins, Centro Médico Nacional Siglo XXI IMSS, JM Ramos Mejia CABA, Hospital de Transplantes Euryclides de Jesus Zerbini, Hospital Universitário Walter Cantídio, Universidade Federal do Paraná (UFPR), Universidade de São Paulo (USP), Bueras, Centro de Pesquisas Oncológicas, Hospital dos Fornecedores de Cana de Piracicaba, Hospital AC Camargo Cancer Center, Universidade Federal Fluminense (UFF), Fundaleu, Hospital Jorge Valente, Hospital Santa Casa de Misericordia de Maceió, Hospital Santa Marcelina, Universidade Estadual Paulista (UNESP), and Hemorio
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Male ,Cancer Research ,medicine.medical_specialty ,Coronavirus disease 2019 (COVID-19) ,medicine.medical_treatment ,Hematopoietic stem cell transplantation ,SARS-COV-2 ,survival ,COVID-19 Testing ,chronic myeloid leukemia ,Internal medicine ,Leukemia, Myelogenous, Chronic, BCR-ABL Positive ,medicine ,Humans ,In patient ,business.industry ,SARS-CoV-2 ,Myeloid leukemia ,COVID-19 ,molecular response ,Hematology ,medicine.disease ,Comorbidity ,Latin America ,Oncology ,Multicenter study ,Major Molecular Response ,business ,Tyrosine kinase - Abstract
Made available in DSpace on 2022-04-29T08:45:36Z (GMT). No. of bitstreams: 0 Previous issue date: 2021-01-01 This observational, multicenter study aimed to report the clinical evolution of COVID-19 in patients with chronic myeloid leukemia in Latin America. A total of 92 patients presented with COVID-19 between March and December 2020, 26% of whom were severe or critical. The median age at COVID-19 diagnosis was 48 years (22–79 years), 32% were 60 years or older, and 61% were male. Thirty-nine patients presented with at least one comorbidity (42.3%). Eighty-one patients recovered (88%), and 11 (11.9%) died from COVID-19. There was one case of reinfection. Patients with a major molecular response presented superior overall survival compared to patients with no major molecular response (91 vs. 61%, respectively; p = 0.004). Patients in treatment-free remission and receiving tyrosine kinase inhibitors showed higher survival rates than patients who underwent hematopoietic stem cell transplantation and those who did not receive tyrosine kinase inhibitors (100, 89, 50, and 33%, respectively; p < 0.001). Hematology and Hemotherapy Center University of Campinas Hospital Nacional Edgardo Rebagliati Martins Centro Médico Nacional Siglo XXI IMSS JM Ramos Mejia CABA Hospital de Transplantes Euryclides de Jesus Zerbini Faculdade de Medicina da Universidade Federal do Ceará Hospital Universitário Walter Cantídio Complexo Hospital de Clínicas–Universidade Federal do Paraná Laboratory of Medical Investigation in Pathogenesis and targeted therapy in Onco-Immuno-Hematology (LIM/31) Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo Hospital de Valdivia Bueras Centro de Pesquisas Oncológicas Hospital dos Fornecedores de Cana de Piracicaba Hospital AC Camargo Cancer Center Hospital Universitário Antonio Pedro Universidade Federal Fluminense Hospitalization & Clinical Research Center Fundaleu Hospital Jorge Valente Hospital Santa Casa de Misericordia de Maceió Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto University of São Paulo Hospital Santa Marcelina São Paulo State University UNESP Medical School Campus de Botucatu Hemorio São Paulo State University UNESP Medical School Campus de Botucatu
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- 2021
6. A IMPORTÂNCIA DA APLICAÇÃO DO ESCORES PROGNÓSTICOS DIPPS E DIPPS PLUS E O PAPEL DO CARIÓTIPO NESSA APLICAÇÃO EM UM GRUPO DE PACIENTES BRASILEIROS COM MIELOFIBROSE
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Fernanda S Seguro, Katia B Pagnano, R.S. Taavares, Israel Bendit, Renato Centrone, Ackvd Nascimento, Nelma D Clementino, Monika Conchon, and Solange Alves Santana
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business.industry ,lcsh:RC633-647.5 ,Immunology and Allergy ,Medicine ,Hematology ,lcsh:Diseases of the blood and blood-forming organs ,business ,Humanities - Published
- 2020
7. NTAL is associated with treatment outcome, cell proliferation and differentiation in acute promyelocytic leukemia
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L. M. Sobral, Armand Keating, Fabiola Traina, Carolina Hassibe Thomé, Rosane Bittencourt, Francesco Lo-Coco, Cesar Ortiz, Evandro M. Fagundes, Miguel A. Sanz, Martin S. Tallman, Luisa C A Koury, Richard Dillon, Maria de Lourdes Lopes Ferrari Chauffaille, Ana Beatriz F. Gloria, Douglas R. A. Silveira, Vitor M. Faça, Guilherme A. dos Santos, Arnold Ganser, Cleide Lúcia Araújo Silva, Ricardo Pasquini, Fabio R. Kerbauy, Nancy Berliner, Eduardo Magalhães Rego, E.C. Nunes, Andréia Machado Leopoldino, Cristiane Damas Gil, Diego A Pereira-Martins, Katia B Pagnano, Bob Löwenberg, Juan L Coelho-Silva, Priscila Santos Scheucher, Raul Antônio Morais Melo, Peter J. M. Valk, Germano Aguiar Ferreira, Raul C. Ribeiro, Lucas Eduardo Botelho de Souza, and Hematology
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0301 basic medicine ,Male ,Cell ,Apoptosis ,chemistry.chemical_compound ,Prognostic markers ,Leukocyte Count ,Mice ,0302 clinical medicine ,Leukemia, Promyelocytic, Acute ,Bone Marrow ,Antineoplastic Combined Chemotherapy Protocols ,Anthracyclines ,Arsenic trioxide ,Multidisciplinary ,Cell Differentiation ,Middle Aged ,ESTUDOS RETROSPECTIVOS ,Leukemia ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,Gene Knockdown Techniques ,Medicine ,Female ,Cell activation ,Acute promyelocytic leukemia ,Adult ,Adolescent ,Cell Survival ,Science ,Tretinoin ,Biology ,Article ,Acute myeloid leukaemia ,Disease-Free Survival ,03 medical and health sciences ,Young Adult ,Membrane Microdomains ,Cell Line, Tumor ,medicine ,Animals ,Humans ,Protein kinase B ,PI3K/AKT/mTOR pathway ,Adaptor Proteins, Signal Transducing ,Aged ,Cell Proliferation ,Retrospective Studies ,Cell growth ,medicine.disease ,Survival Analysis ,Xenograft Model Antitumor Assays ,030104 developmental biology ,chemistry ,Cancer research - Abstract
Non-T cell activation linker (NTAL) is a lipid raft-membrane protein expressed by normal and leukemic cells and involved in cell signaling. In acute promyelocytic leukemia (APL), NTAL depletion from lipid rafts decreases cell viability through regulation of the Akt/PI3K pathway. The role of NTAL in APL cell processes, and its association with clinical outcome, has not, however, been established. Here, we show that reduced levels of NTAL were associated with increased all-trans retinoic acid (ATRA)-induced differentiation, generation of reactive oxygen species, and mitochondrial dysfunction. Additionally, NTAL-knockdown (NTAL-KD) in APL cell lines led to activation of Ras, inhibition of Akt/mTOR pathways, and increased expression of autophagy markers, leading to an increased apoptosis rate following arsenic trioxide treatment. Furthermore, NTAL-KD in NB4 cells decreased the tumor burden in (NOD scid gamma) NSG mice, suggesting its implication in tumor growth. A retrospective analysis of NTAL expression in a cohort of patients treated with ATRA and anthracyclines, revealed that NTAL overexpression was associated with a high leukocyte count (P = 0.007) and was independently associated with shorter overall survival (Hazard Ratio: 3.6; 95% Confidence Interval: 1.17–11.28; P = 0.026). Taken together, our data highlights the importance of NTAL in APL cell survival and response to treatment.
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- 2020
8. COVID-19 IN CHRONIC MYELOID LEUKEMIA PATIENTS – BRAZILIAN EXPERIENCE
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Natália N Gonçalves, Luciana Correa Oliveira de Oliveira, Renato Centrone, Jaisson Bortolini, Israel Bendit, André L G Lourenço, Gustavo Hr Magalhaes, Katia B Pagnano, Fabio Moore Nucci, Leila Martins Perobelli, Nelma D Clementino, Fabio Ps Santos, Acy Telles de Souza Quixadá, Ana Carolina Mourão Toreli, Jaqueline Sapelli, LC Palma, Muriel Silva Moura, Renato Tavares, Fernanda S Seguro, Monika Conchon, Vam Funke, Paula de Oliveira Montandon Hokama, Marcia Torresan Delamain, Carla Boquimpani, and Laura Fogliatto
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medicine.medical_specialty ,Immunology ,632.Chronic Myeloid Leukemia: Therapy ,Biochemistry ,chemistry.chemical_compound ,Internal medicine ,medicine ,Immunology and Allergy ,business.industry ,lcsh:RC633-647.5 ,Ponatinib ,Imatinib ,Cell Biology ,Hematology ,lcsh:Diseases of the blood and blood-forming organs ,medicine.disease ,Comorbidity ,Pulmonary hypertension ,Hematologic Response ,Discontinuation ,Dasatinib ,chemistry ,Nilotinib ,business ,medicine.drug - Abstract
Coronavirus disease (COVID-19) is an infectious disease caused by the newly discovered coronavirus Sars-Cov2. In Brazil, the first COVID-19 case was diagnosed in February 2020, and since then, the number of cases and deaths has increased exponentially, reaching 2.610.102 confirmed cases and 91.263 deaths on July 31st. Most people have a mild to moderate respiratory illness, but the clinical evolution may be severe in older adults and patients with comorbidities, such as cancer. There are few reports of COVID-19 in patients with chronic myeloid leukemia (CML). This ongoing study aims to collect data about COVID-19 in CML patients from Brazil and their outcomes. Methods: This is an observational, multicentric, ongoing register study. Hematologists from private and public CML reference centers from different regions of Brazil were invited to report their cases of COVID-19 in CML patients. Altogether, those centers are responsible for the care of approximately 4336 CML patients. COVID-19 was classified as mild/moderate, severe (defined as tachypnoea [≥30 breaths per min], oxygen saturation ≤93% at rest, or PaO2/FiO2 ratio Results: Between March and July 2020, 24 institutions contributed to this analysis, and reported 28 COVID-19 cases in CML patients. Eighteen centers were from the South and Southeast regions, 5 from Northeast, and one from the Central region. There were 19 cases (67.9%) from the Southeast region, 8 (28.6%) from the Northeast, one from South (3.6%). The median age was 54 years (24-79), with 13 (44%) older than 60. Male patients were predominant (67.9%). There was one patient in the accelerated phase. There were two cases of COVID-19 simultaneous to CML diagnosis, 10 using imatinib, 7 dasatinib, 6 nilotinib, one ponatinib, one asciminib, and one patient in treatment-free remission after imatinib discontinuation. The median time of CML diagnosis was 7.0 years (0-26). Current CML response was: no hematologic response (n=8), hematologic response (n=4), major molecular response (n=9), MR4.0 or MR5.0 (n= 7). Eleven patients interrupted treatment temporarily during COVID. COVID-19 was confirmed by RT-PCR of oral and nasal swab collection (20) or serologic test (07). One case is suspect, awaiting confirmation. The majority of the patients presented at least one comorbidity (60%): hypertension (7), diabetes (3), chronic renal failure (1), dyslipidemia (2), arterial disease (2), cirrhosis (1), chronic obstructive pulmonary disease/emphysema (2), pulmonary hypertension (1), HTLV1 (1), obesity (n=1). COVID-19 severity: mild/moderate (19), severe/critic (9). Five out of 9 (55%) of the severe/critic cases were older than 60, 4/9 presented comorbidities and 5/9 (55%) had no major molecular response (MMR)(one was in accelerated phase, one newly diagnosed, and 3 with only hematologic response). Among the mild/moderate cases, 12/19 had optimal response (63%) and 7/19 (36%) had no hematologic response. Twenty-one patients recovered, 4 are still hospitalized, and 3 died from COVID: one newly diagnosed case with high leukocytes counts and with a simultaneous bacterial infection, one elderly patient with comorbidities treated with imatinib and one patient treated with nilotinib, with hematologic response. A fourth patient in the accelerated phase died 2 months after discharge, from disease progression and pulmonary infection. Conclusion: Although the sample size is still small to make conclusions regarding COVID-19 behavior in CML patients, the most severe cases occurred in patients not in MMR. The continued register of the cases will increase our knowledge about this disease and how to manage these patients. Disclosures Pagnano: Astellas: Other: Advisory Board and lecture; Novartis: Other: Advisory Board; EMS: Other: Lecture; Pintpharma: Other: Lecture. Magalhães:AstraZeneca: Speakers Bureau; Novartis: Speakers Bureau. Santos:Novartis: Other: Speaker fee; Bristol-Myers Squibb: Other: Speaker fee. Clementino:EMS: Other: Financial support for congress.
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- 2020
9. Age-adjusted international prognostic index is a predictor of survival in gastric diffuse B-cell non-Hodgkin lymphoma patients
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Joana M. P. Desterro, Maria Gomes da Silva, Carlos S. Chiattone, Marcia Torresan Delamain, Katia B Pagnano, Francesco Merli, Massimo Federico, Stefano Luminari, Anna Fedina, Carmino Antonio De Souza, and Eliana C M Miranda
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0301 basic medicine ,medicine.medical_specialty ,Abdominal pain ,Anemia ,Gastroenterology ,03 medical and health sciences ,0302 clinical medicine ,International Prognostic Index ,Internal medicine ,Gastric ,Diffuse large B-cell lymphoma ,Prognosis ,Hematology ,medicine ,lcsh:RC633-647.5 ,business.industry ,Proportional hazards model ,Gastric lymphoma ,lcsh:Diseases of the blood and blood-forming organs ,medicine.disease ,Lymphoma ,Surgery ,030104 developmental biology ,030220 oncology & carcinogenesis ,B-Cell Non-Hodgkin Lymphoma ,Original Article ,medicine.symptom ,business - Abstract
BACKGROUND: The clinical course of gastric lymphoma is heterogeneous and clinical symptoms and some factors have been related to prognosis. OBJECTIVE: The present study aims to identify prognostic factors in gastric diffuse B-cell non-Hodgkin lymphoma diagnosed and treated in different countries. METHODS: A consecutive series of gastric diffuse B-cell non-Hodgkin lymphoma patients diagnosed and treated in Brazil, Portugal and Italy, between February 2008 and December 2014 was evaluated. RESULTS: Of 104 patients, 57 were female and the median age was 69 years (range: 28-88). The distribution of the age-adjusted international prognostic index was 12/95 (13%) high risk, 20/95 (21%) high-intermediate risk and 63/95 (66%) low/low-intermediate risk. Symptoms included abdominal pain (63/74), weight loss (57/73), dysphagia (37/72) and nausea/vomiting (37/72). Bulky disease was found in 24% of the cases, anemia in 33 of 76 patients and bleeding in 22 of 72 patients. The median follow-up time was 25 months (range: 1-77 months), with 1- and 5-year survival rates of 79% and 76%, respectively. The multivariate Cox Regression identified the age-adjusted international prognostic index as a predictor of death (hazard risk: 3.62; 95% confidence interval: 2.21-5.93; p-value
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- 2016
10. Feasibility of minimal residual disease studies by multiparametric flow cytometry for acute myeloid leukemia in a developing country
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Marcos Roberto Pedron Oltramari, Marcia Higashi, Ana Silvia Gouvêa de Lima, Maria Isabel A. Madeira, Lorena Lobo de Figueiredo-Pontes, Dario Campana, Rosane Bittencourt, Maria de Lourdes Lopes Ferrari Chauffaille, Katia B Pagnano, Fabiola Traina, Rodrigo Miguel Bendlin, Elaine Coustan-Smith, Ronald Pallota, Priscila Santos Scheucher, Luisa Koury Corrêa de Araujo, and Eduardo Magalhães Rego
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Oncology ,medicine.medical_specialty ,biology ,medicine.diagnostic_test ,Genetic heterogeneity ,business.industry ,Developing country ,Myeloid leukemia ,Hematology ,Minimal residual disease ,Global Capacity-Building Showcase ,Flow cytometry ,03 medical and health sciences ,0302 clinical medicine ,hemic and lymphatic diseases ,030220 oncology & carcinogenesis ,Internal medicine ,biology.protein ,Medicine ,In patient ,Antibody ,business ,030215 immunology - Abstract
Despite the improved results achieved with dose-intense treatments, the prognosis of acute myeloid leukemia (AML) patients remains poor, with cure rates ranging from 60% to 70% in patients
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- 2017
11. BCR-ABL1-induced downregulation of WASP in chronic myeloid leukemia involves epigenetic modification and contributes to malignancy
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Gareth E. Jones, Katia B Pagnano, Fabíola Attié de Castro, Beatriz F Ribeiro, Nelson Hamerschlak, Luiz Roberto Sardinha, Maria Emilia Zenteno, Yolanda Calle, Jacqueline F. Jacysyn, Daniel D. De Carvalho, Gustavo P. Amarante-Mendes, Maria Aparecida Zanichelli, and Welbert Oliveira Pereira
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0301 basic medicine ,Cancer Research ,Carcinogenesis ,Immunology ,Fusion Proteins, bcr-abl ,Antineoplastic Agents ,Apoptosis ,macromolecular substances ,Biology ,medicine.disease_cause ,Epigenesis, Genetic ,TNF-Related Apoptosis-Inducing Ligand ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,0302 clinical medicine ,Leukemia, Myelogenous, Chronic, BCR-ABL Positive ,hemic and lymphatic diseases ,medicine ,Journal Article ,Humans ,Epigenetics ,Promoter Regions, Genetic ,Protein Kinase Inhibitors ,Myeloid leukemia ,Cell Biology ,DNA Methylation ,medicine.disease ,3. Good health ,Leukemia ,Haematopoiesis ,030104 developmental biology ,Drug Resistance, Neoplasm ,030220 oncology & carcinogenesis ,DNA methylation ,Cancer research ,Azacitidine ,Imatinib Mesylate ,Original Article ,Tyrosine kinase ,Wiskott-Aldrich Syndrome Protein ,K562 cells ,Signal Transduction - Abstract
Chronic myeloid leukemia (CML) is a myeloproliferative disease caused by the BCR–ABL1 tyrosine kinase (TK). The development of TK inhibitors (TKIs) revolutionized the treatment of CML patients. However, TKIs are not effective to those at advanced phases when amplified BCR–ABL1 levels and increased genomic instability lead to secondary oncogenic modifications. Wiskott–Aldrich syndrome protein (WASP) is an important regulator of signaling transduction in hematopoietic cells and was shown to be an endogenous inhibitor of the c-ABL TK. Here, we show that the expression of WASP decreases with the progression of CML, inversely correlates with the expression of BCR–ABL1 and is particularly low in blast crisis. Enforced expression of BCR–ABL1 negatively regulates the expression of WASP. Decreased expression of WASP is partially due to DNA methylation of the proximal WASP promoter. Importantly, lower levels of WASP in CML advanced phase patients correlate with poorer overall survival (OS) and is associated with TKI response. Interestingly, enforced expression of WASP in BCR–ABL1-positive K562 cells increases the susceptibility to apoptosis induced by TRAIL or chemotherapeutic drugs and negatively modulates BCR–ABL1-induced tumorigenesis in vitro and in vivo. Taken together, our data reveal a novel molecular mechanism that operates in BCR–ABL1-induced tumorigenesis that can be used to develop new strategies to help TKI-resistant, CML patients in blast crisis (BC).
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- 2017
12. BCR-ABL1 level monitoring in chronic myeloid leukemia by real time polymerase chain reaction in Brazil - not so real
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Katia B Pagnano
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business.industry ,lcsh:RC633-647.5 ,Myeloid leukemia ,Hematology ,lcsh:Diseases of the blood and blood-forming organs ,Virology ,Scientific Comment ,03 medical and health sciences ,Bcr abl1 ,0302 clinical medicine ,Real-time polymerase chain reaction ,030220 oncology & carcinogenesis ,Medicine ,business ,030215 immunology - Published
- 2017
13. Inflammatory picture of Philadelphia-negative myeloproliferative neoplasms☆
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Katia B Pagnano
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Philadelphia negative ,medicine.medical_specialty ,business.industry ,MEDLINE ,Hematology ,Dermatology ,03 medical and health sciences ,0302 clinical medicine ,030220 oncology & carcinogenesis ,Scientific comment ,Immunology and Allergy ,Medicine ,business ,030215 immunology - Published
- 2018
14. High Δnp73/TAp73 ratio is associated with poor prognosis in acute promyelocytic leukemia
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Miguel A. Sanz, Francesco Lo-Coco, David Grimwade, Rodrigo Miguel Bendlin, Cristina Bortolheiro, Carlos S. Chiattone, Juan L Coelho-Silva, Carmino Antonio De Souza, Melina Athayde, Antonio R. Lucena-Araujo, Martin S. Tallman, Rafael H. Jacomo, Stanley L. Schrier, Katia B Pagnano, Ana Beatriz F. Gloria, Maria de Lourdes Lopes Ferrari Chauffaille, Ricardo Pasquini, Rosane Bittencourt, Raul Antônio Morais Melo, Ingrid Mito, Carolina Hassibe Thomé, Haesook T. Kim, Raul C. Ribeiro, Nancy Berliner, Bob Löwenberg, Arnold Ganser, Eduardo Magalhães Rego, and Hematology
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Male ,medicine.medical_treatment ,Retinoic acid ,medicine.disease_cause ,Biochemistry ,chemistry.chemical_compound ,Leukemia, Promyelocytic, Acute ,immune system diseases ,Models ,Protein Isoforms ,Child ,Promyelocytic ,Leukemic ,Myeloid Neoplasia ,Leukemia ,Gene Expression Regulation, Leukemic ,Hazard ratio ,Nuclear Proteins ,Hematology ,Adolescent ,Adult ,Aged ,DNA-Binding Proteins ,Disease-Free Survival ,Female ,Humans ,Middle Aged ,Proportional Hazards Models ,Survival Rate ,Tumor Suppressor Proteins ,Alternative Splicing ,Models, Biological ,Acute promyelocytic leukemia ,HEMATOLOGIA ,Immunology ,Biology ,Acute ,SDG 3 - Good Health and Well-being ,medicine ,neoplasms ,Survival rate ,Chemotherapy ,Proportional hazards model ,Tumor Protein p73 ,Cell Biology ,medicine.disease ,Biological ,chemistry ,Gene Expression Regulation ,Cancer research ,Ovarian cancer ,Carcinogenesis ,Settore MED/15 - Malattie del Sangue - Abstract
The TP73 gene transcript is alternatively spliced and translated into the transcriptionally active (TAp73) or inactive (Delta Np73) isoforms, with opposite effects on the expression of p53 target genes and on apoptosis induction. The imbalance between Delta Np73 and TAp73 may contribute to tumorigenesis and resistance to chemotherapy in human cancers, including hematologic malignancies. In acute promyelocytic leukemia (APL), both isoforms are expressed, but their relevance in determining response to therapy and contribution to leukemogenesis remains unknown. Here, we provide the first evidence that a higher Delta Np73/TAp73 RNA expression ratio is associated with lower survival, lower disease-free survival, and higher risk of relapse in patients with APL homogeneously treated with all-trans retinoic acid and anthracycline-based chemotherapy, according to the International Consortium on Acute Promyelocytic Leukemia (IC-APL) study. Cox proportional hazards modeling showed that a high Delta Np73/TAp73 ratio was independently associated with shorter overall survival (hazard ratio, 4.47; 95% confidence interval, 1.64-12.2; P = .0035). Our data support the hypothesis that the Delta Np73/TAp73 ratio is an important determinant of clinical response in APL and may offer a therapeutic target for enhancing chemosensitivity in blast cells.
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- 2015
15. Prognostic impact of KMT2E transcript levels on outcome of patients with acute promyelocytic leukaemia treated with all-trans retinoic acid and anthracycline-based chemotherapy: An International Consortium on Acute Promyelocytic Leukaemia study
- Author
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Francesco Lo-Coco, Miguel A. Sanz, David Grimwade, Evandro M. Fagundes, Charlotte M. Niemeyer, Haesook T. Kim, Robert E. Gallagher, Raul A. M. Melo, Nancy Berliner, Martin S. Tallman, Hau C. Kwaan, Antonio R. Lucena-Araujo, Ana Carolina Stocco de Lima, Stanley L. Schrier, Katia B Pagnano, Rosane Bittencourt, Rafael H. Jacomo, Raul C. Ribeiro, Maria de Lourdes Lopes Ferrari Chauffaille, Ricardo Pasquini, Carlos S. Chiattone, Bob Löwenberg, Arnold Ganser, Eduardo Magalhães Rego, and Hematology
- Subjects
Oncology ,Adult ,Male ,medicine.medical_specialty ,Anthracycline ,acute promyelocytic leukaemia ,Adolescent ,KMT2E (MLL5) ,medicine.medical_treatment ,Retinoic acid ,Tretinoin ,Acute ,International Consortium on Acute Promyelocytic Leukaemia ,chemistry.chemical_compound ,Young Adult ,Leukemia, Promyelocytic, Acute ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Humans ,Cumulative incidence ,Anthracyclines ,Promyelocytic ,Chemotherapy ,Univariate analysis ,Leukemia ,business.industry ,Hazard ratio ,Hematology ,Odds ratio ,developing countries ,Middle Aged ,all-trans retinoic acid ,DNA-Binding Proteins ,Haematopoiesis ,Treatment Outcome ,chemistry ,Case-Control Studies ,Immunology ,Female ,business ,Settore MED/15 - Malattie del Sangue - Abstract
The KMT2E (MLL5) gene encodes a histone methyltransferase implicated in the positive control of genes related to haematopoiesis. Its close relationship with retinoic acid-induced granulopoiesis suggests that the deregulated expression of KMT2E might lead acute promyelocytic leukaemia (APL) blasts to become less susceptible to the conventional treatment protocols. Here, we assessed the impact of KMT2E expression on the prognosis of 121 APL patients treated with ATRA and anthracycline-based chemotherapy. Univariate analysis showed that complete remission (P = 0.006), 2-year overall survival (OS) (P = 0.005) and 2-year disease-free survival (DFS) rates (P = 0.037) were significantly lower in patients with low KMT2E expression; additionally, the 2-year cumulative incidence of relapse was higher in patients with low KMT2E expression (P = 0.04). Multivariate analysis revealed that low KMT2E expression was independently associated with lower remission rate (odds ratio [OR]: 7.18, 95% confidence interval [CI]: 1.71-30.1; P = 0.007) and shorter OS (hazard ratio [HR]: 0.27, 95% CI: 0.08-0.87; P = 0.029). Evaluated as a continuous variable, KMT2E expression retained association with poor remission rate (OR: 10.3, 95% CI: 2.49-43.2; P = 0.001) and shorter survival (HR: 0.17, 95% IC: 0.05-0.53; P = 0.002), while the association with DFS was of marginal significance (HR: 1.01; 95% CI: 0.99-1.02; P = 0.06). In summary, low KMT2E expression may predict poor outcome in APL patients.
- Published
- 2014
16. Guidelines on the diagnosis and treatment for acute promyelocytic leukemia: Associacao Brasileira de Hematologia, Hemoterapia e Terapia Celular Guidelines Project: Associacao Medica Brasileira - 2013
- Author
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Evandro M. Fagundes, Rosane Bittencourt, Sandra Serson Rohr, Raul A. M. Melo, Wanderley Marques Bernardo, Eduardo Magalhães Rego, Rafael H. Jacomo, Katia B Pagnano, Maria de Lourdes Lopes Ferrari Chauffaille, Ana Beatriz Firmato, Universidade Estadual de Campinas (UNICAMP), Universidade de São Paulo (USP), Universidade Federal de São Paulo (UNIFESP), Universidade de Brasilia, Universidade Federal do Rio Grande do Sul, Universidade Federal de Minas Gerais, and Universidade Federal de Pernambuco
- Subjects
Gerontology ,Acute promyelocytic leukemia ,medicine.medical_specialty ,lcsh:RC633-647.5 ,business.industry ,MEDLINE ,lcsh:Diseases of the blood and blood-forming organs ,Hematology ,medicine.disease ,LEUCEMIA MIELOIDE AGUDA (DIAGNÓSTICO ,TRATAMENTO) ,Internal medicine ,medicine ,Special article ,Leucemia ,business - Abstract
The guidelines project is a joint initiative of the Associação Médica Brasileira and the Conselho Federal de Medicina. It aims to collect information to standardize decisions and help create strategies during diagnosis and treatment. These data were prepared and are recommended by the Associação Brasileira de Hematologia, Hemoterapia e Terapia Celular (ABHH). Even so, all possible decisions should be evaluated by the physician responsible for diagnosis and treatment according to the patient's setting and clinical status.
- Published
- 2014
17. Conventional chemotherapy for acute myeloid leukemia: a Brazilian experience
- Author
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Rossini Ms, Irene Lorand-Metze, Katia B Pagnano, Takahashi T, de Souza Ca, Afonso Celso Vigorito, Gislaine B. Oliveira, Fabiola Traina, and E.C.M. Miranda
- Subjects
Acute promyelocytic leukemia ,Adult ,Male ,medicine.medical_specialty ,Transplante de medula óssea ,Adolescent ,Bone marrow transplantation ,Survival ,lcsh:Medicine ,Context (language use) ,Disease-Free Survival ,Statistics, Nonparametric ,Leukemia, Promyelocytic, Acute ,Internal medicine ,hemic and lymphatic diseases ,Antineoplastic Combined Chemotherapy Protocols ,Sobrevida ,medicine ,Hemotherapy ,Humans ,Chemotherapy ,Survival rate ,neoplasms ,Retrospective Studies ,Acute myeloid leukemia ,business.industry ,Mortality rate ,Remission Induction ,lcsh:R ,Myeloid leukemia ,Retrospective cohort study ,General Medicine ,Middle Aged ,medicine.disease ,Surgery ,Survival Rate ,Leucemia mielóide aguda ,Leukemia ,Leukemia, Myeloid ,Acute Disease ,Female ,Quimioterapia ,business ,Brazil ,Follow-Up Studies - Abstract
CONTEXT: Young patients affected by acute myeloid leukemia (AML) achieve complete remission (CR) using conventional chemotherapy in about 55-85%. However, 30% of patients fail to achieve CR and the remission duration is often only about 12 months. More intensive treatment after CR seems to be necessary in order to maintain CR and obtain a definitive cure. In Brazil, few reports have been published on this important subject. OBJECTIVE: The aim of this study was to describe a Brazilian experience in the treatment of "de novo" acute myeloid leukemia (AML) in younger adult patients (age < 60 years). DESIGN: Retrospective analysis. SETTING: University Hospital, Hematology and Hemotherapy Center, State University of Campinas, Brazil. PARTICIPANTS: Newly diagnosed cases of "de novo" AML in the period from January 1994 to December 1998 were evaluated retrospectively, in relation to response to treatment, overall survival (OS) and disease free survival (DFS). Cases with acute promyelocytic leukemia (APL) were also included in this analysis. RESULTS: On the basis of an intention to treat, 78 cases of AML, including 17 cases of APL, were evaluated. The overall median follow-up was 272 days. The complete remission (CR) rate was 63.6% in the AML group (excluding APL) and 78% in the APL group. The 5-year estimated disease-free survival (DFS) was 80% for the APL group and 34% for the AML group (P = 0.02). The 5-year estimated overall survival (OS) was 52% for the APL group and 20.5% for the AML group, respectively (P = NS). Relapse was observed in 12/39 (30.7%) patients with AML and 1/11 (9%) with APL. CONCLUSIONS: These results are similar to those reported in the literature. However, relapse and mortality rates remain high, and a search for more aggressive strategies in order to prevent relapse is recommended. CONTEXTO: Pacientes adultos com diagnóstico de leucemia mielóide aguda (LMA) obtém remissão completa (RC) com quimioterapia convencional em cerca de 55-85% dos casos, e a sua duração é de aproximadamente 12 meses. Cerca de 30% dos pacientes não atingem a RC. Para manter a RC e obter cura definitiva parece ser necessário intensificar o tratamento após a RC. No Brasil, há um pequeno número de artigos publicados a esse respeito. OBJETIVO: Descrever a experiência brasileira no tratamento de leucemia mielóide aguda "de novo" em jovens e adultos com idade inferior a 60 anos. TIPO DE ESTUDO: Análise retrospectiva. LOCAL: Hospital das Clínicas e Hemocentro da Universidade Estadual de Campinas. PARTICIPANTES: Foram estudados, retrospectivamente, casos novos de LMA entre 1994 e 1998, com relação à resposta ao tratamento de quimioterapia, sobrevida global e sobrevivência livre de doença. RESULTADOS: Entraram no estudo 78 pacientes de LMA, incluindo 17 casos de leucemia promielocítica (LPM). A média de seguimento foi de 272 dias. A taxa de RC foi de 63,6% nos pacientes com LMA excluindo-se os pacientes com LPM, e 78% nos pacientes com LPM. A sobrevida livre de doença em 5 anos foi de 80% nos pacientes com LPM e 34% para os pacientes com LMA (P=0,01). A sobrevida global foi de 52% e 20,5% para os pacientes com LPM e LMA respectivamente (P=NS). Recidiva foi observada em 12/39 (30,7%) dos pacientes com LMA e 1/11 (9%) na LPM. CONCLUSÕES: Esses resultados são semelhantes aos encontrados na literatura, entretanto, o número de recidivas e a mortalidade mantém-se alta, recomendando-se pesquisa de estratégias mais agressivas para prevenir recidivas.
- Published
- 2000
18. Primary myelofibrosis: risk stratification by IPSS identifies patients with poor clinical outcome
- Author
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Carmino Antonio De Souza, Daiane de Almeida, Irene Lorand-Metze, Gislaine B. Oliveira, Carolina Silva Costa Lima, José Vassallo, Katia B Pagnano, Marcia Torresan Delamain, and Bruno Deltreggia Benites
- Subjects
Adult ,Male ,Pediatrics ,medicine.medical_specialty ,Risk Assessment ,Severity of Illness Index ,Prognostic score ,Risk groups ,Predictive Value of Tests ,Risk Factors ,Internal medicine ,Severity of illness ,Humans ,Medicine ,Treatment Failure ,Myelofibrosis ,Aged ,Aged, 80 and over ,lcsh:R5-920 ,business.industry ,IPSS ,Jak2 mutation ,Reproducibility of Results ,General Medicine ,Janus Kinase 2 ,Middle Aged ,Clinical Science ,medicine.disease ,Prognosis ,Primary Myelofibrosis ,Predictive value of tests ,Risk stratification ,Female ,lcsh:Medicine (General) ,business ,Risk assessment - Abstract
OBJECTIVES: To evaluate whether risk scores used to classify patients with primary myelofibrosis and JAK-2 V617F mutation status can predict clinical outcome. METHODS: A review of clinical and laboratory data from 74 patients with primary myelofibrosis diagnosed between 1992 and 2011. The IPSS and Lille scores were calculated for risk stratification and correlated with overall survival. RESULTS: A V617F JAK2 mutation was detected in 32 cases (47%), with no significant correlation with overall survival. The patients were classified according to the scores: Lille - low, 53 (73.%); intermediate, 13 (18%); and high, 5 (7%); and IPSS – low, 15 (26%); intermediate-1, 23 (32%); intermediate-2, 19 (26%); and high, 15 (31%). Those patients presenting a higher risk according to the IPSS (high and intermediate-2) had a significantly shorter overall survival relative to the low risk groups (intermediate-1 and low) (p = 0.02). CONCLUSIONS: These results emphasize the importance of the IPSS prognostic score for risk assessment in predicting the clinical outcome of primary myelofibrosis patients.
- Published
- 2013
19. Molecular characteristics and chromatin texture features in acute promyelocytic leukemia
- Author
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Fernando Ferreira Costa, Katia B Pagnano, Mariana R. B. Mello, Fernanda Gonçalves Pereira-Cunha, Dulcineia M. Albuquerque, Krizzia Borges Albanez, Irene Lorand-Metze, and Konradin Metze
- Subjects
Male ,Pathology ,DNA Mutational Analysis ,Leukocyte Count ,Immunophenotyping ,Leukemia, Promyelocytic, Acute ,Prospective Studies ,Aged, 80 and over ,Nuclear Proteins ,General Medicine ,Methylation ,Middle Aged ,Prognosis ,Chromatin ,DNA-Binding Proteins ,Leukemia ,Fractals ,Promyelocytic leukemia ,DNA methylation ,Female ,Nucleophosmin ,lcsh:RB1-214 ,Adult ,Acute promyelocytic leukemia ,NPM1 ,medicine.medical_specialty ,Histology ,FLT3-ITD ,Biology ,Pathology and Forensic Medicine ,Young Adult ,Predictive Value of Tests ,Biomarkers, Tumor ,medicine ,lcsh:Pathology ,Humans ,Cyclin-Dependent Kinase Inhibitor p16 ,Aged ,Cyclin-Dependent Kinase Inhibitor p15 ,Proportional Hazards Models ,Tumor Suppressor Proteins ,Research ,Tumor Protein p73 ,DNA Methylation ,Chromatin Assembly and Disassembly ,medicine.disease ,fms-Like Tyrosine Kinase 3 ,Mutation ,Fms-Like Tyrosine Kinase 3 ,Chromatin texture - Abstract
Background Acute promyelocytic leukemia is a cytogenetically well defined entity. Nevertheless, some features observed at diagnosis are related to a worse outcome of the patients. Methods In a prospective study, we analyzed peripheral (PB) leukocyte count, immunophenotype, methylation status of CDKN2B, CDKN2A and TP73; FLT3 and NPM1 mutations besides nuclear chromatin texture characteristics of the leukemic cells. We also examined the relation of these features with patient’s outcome. Results Among 19 cases, 4 had a microgranular morphology, 7 presented PB leukocytes >10x109/l, 2 had FLT3-ITD and 3 had FLT3-TKD (all three presenting a methylated CDKN2B). NPM1 mutation was not observed. PB leukocyte count showed an inverse relation with standard deviation of gray levels, contrast, cluster prominence, and chromatin fractal dimension (FD). Cases with FLT3-ITD presented a microgranular morphology, PB leukocytosis and expression of HLA-DR, CD34 and CD11b. Concerning nuclear chromatin texture variables, these cases had a lower entropy, contrast, cluster prominence and FD, but higher local homogeneity, and R245, in keeping with more homogeneously distributed chromatin. In the univariate Cox analysis, a higher leukocyte count, FLT3-ITD mutation, microgranular morphology, methylation of CDKN2B, besides a higher local homogeneity of nuclear chromatin, a lower chromatin entropy and FD were associated to a worse outcome. All these features lost significance when the cases were stratified for FLT3-ITD mutation. Methylation status of CDNK2A and TP73 showed no relation to patient’s survival. Conclusion in APL, patients with FLT3-ITD mutation show different clinical characteristics and have blasts with a more homogeneous chromatin texture. Texture analysis demonstrated that FLTD-ITD was accompanied not only by different cytoplasmic features, but also by a change in chromatin structure in routine cytologic preparations. Yet we were not able to detect chromatin changes by nuclear texture analysis of patients with the FTLD-TKD or methylation of specific genes.
- Published
- 2012
20. Philadelphia-negative chronic myeloproliferative neoplasms
- Author
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Carlos S. Chiattone, Ana Clara Kneese Virgilio do Nascimento, Maria de Lourdes Lopes Ferrari Chauffaille, Carmino Antonio De Souza, José Vassallo, Rosane Bittencourt, Katia B Pagnano, S. Xavier, Hospital das Clinicas da Universidade Federal do Rio Grande do Sul Hematology Department, Universidade Estadual de Campinas (UNICAMP), Universidade Federal de São Paulo (UNIFESP), Universidade Federal de Minas Gerais Hematology Department, and Faculdade de Ciências Médicas da Santa Casa de São Paulo Hematology Department
- Subjects
IDH1 ,Chronic neutrophilic leukemia ,thrombocytosis ,Review Article ,Philadelphia chromosome ,Polycythemia vera ,polycythemia vera ,hemic and lymphatic diseases ,Medicine ,Myelofibrosis ,Thrombocytosis ,Chronic eosinophilic leukemia ,Trombocitose ,Janus kinase 2 ,biology ,business.industry ,lcsh:RC633-647.5 ,Policitemia vera ,Hematology ,lcsh:Diseases of the blood and blood-forming organs ,medicine.disease ,Myeloproliferative disorders ,Transtornos mieloproliferativos ,myeloproliferative disorders ,Primary myelofibrosis ,Immunology ,biology.protein ,primary myelofibrosis ,business ,Mielofibrose primária - Abstract
Chronic myeloproliferative diseases without the Philadelphia chromosome marker (Ph-), although first described 60 years ago, only became the subject of interest after the turn of the millennium. In 2001, the World Health Organization (WHO) defined the classification of this group of diseases and in 2008 they were renamed myeloproliferative neoplasms based on morphological, cytogenetic and molecular features. In 2005, the identification of a recurrent molecular abnormality characterized by a gain of function with a mutation in the gene encoding Janus kinase 2 (JAK2) paved the way for greater knowledge of the pathophysiology of myeloproliferative neoplasms. The JAK2 mutation is found in 90-98% of polycythemia vera and in about 50% essential thrombocytosis and primary myelofibrosis. In addition to the JAK2 mutation, other mutations involving TET2 (ten-eleven translocation), LNK (a membrane-bound adaptor protein); IDH1/2 (isocitrate dehydrogenase 1/2 enzyme); ASXL1 (additional sex combs-like 1) genes were found in myeloproliferative neoplasms thus showing the importance of identifying molecular genetic alterations to confirm diagnosis, guide treatment and improve our understanding of the biology of these diseases. Currently, polycythemia vera, essential thrombocytosis, myelofibrosis, chronic neutrophilic leukemia, chronic eosinophilic leukemia and mastocytosis are included in this group of myeloproliferative neoplasms, but are considered different situations with individualized diagnostic methods and treatment. This review updates pathogenic aspects, molecular genetic alterations, the fundamental criteria for diagnosis and the best approach for each of these entities. Hospital das Clinicas da Universidade Federal do Rio Grande do Sul Hematology Department Universidade Estadual de Campinas CIPED Laboratory of Experimental Pathology Universidade Federal de São Paulo (UNIFESP) Hematology Department Universidade Federal de Minas Gerais Hematology Department Universidade Estadual de Campinas Hematology Department Faculdade de Ciências Médicas da Santa Casa de São Paulo Hematology Department UNIFESP, Hematology Department SciELO
- Published
- 2012
21. Brazilian experience using high dose sequential chemotherapy followed by autologous hematopoietic stem cell transplantation for malignant lymphomas
- Author
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Eliana C M Miranda, Marcia Torresan Delamain, Carmino Antonio De Souza, Irene Lorand-Metze, Francisco José Penteado, Isabella Salvetti Valente, José Francisco Comenalli Marques, Bruno Kosa Lino Duarte, Renata Baldissera, Afonso Celso Vigorito, Marcio Nucci, Gislaine Oliveira-Duarte, and Katia B Pagnano
- Subjects
Oncology ,medicine.medical_specialty ,Hodgkin disease ,Cyclophosphamide ,Lymphoma ,Hodgkin disease/drug therapy ,medicine.medical_treatment ,Hematopoietic stem cell transplantation ,Cyclophosphamide/administration & dosage ,Nodular sclerosis ,immune system diseases ,Internal medicine ,hemic and lymphatic diseases ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Etoposide ,Chemotherapy ,lcsh:RC633-647.5 ,business.industry ,lcsh:Diseases of the blood and blood-forming organs ,Hematology ,Antineoplastic Combined Chemotherapy Protocols/administration & dosage ,medicine.disease ,Lymphoma, non-Hodgkin ,Surgery ,Regimen ,Transplantation, autologous ,Original Article ,Methotrexate ,business ,medicine.drug - Abstract
OBJECTIVE: To evaluate the use of high-dose sequential chemotherapy in a Brazilian population. METHODS: High-dose cyclophosphamide followed by autologous hematopoietic stem cell transplantation is an effective and feasible therapy for refractory/relapsed lymphomas; this regimen has never before been evaluated in a Brazilian population. All patients (106 with high-grade non-Hodgkin lymphoma and 77 with Hodgkin's lymphoma) submitted to this treatment between 1998 and 2006 were analyzed. Chemotherapy consisted of the sequential administration of high-dose cyclophosphamide (4 or 7 g/m²) and granulocyte-colony stimulating factor (300 µg/day), followed by peripheral blood progenitor cell harvesting, administration of etoposide (2g/m²) and methotrexate (8 g/m² only for Hodgkin's lymphoma) and autologous hematopoietic stem cell transplantation. RESULTS: At diagnosis, non-Hodgkin lymphoma patients had a median age of 45 (range: 8-65) years old, 78% had diffuse large B-cell lymphoma and 83% had stage III/IV disease. The Hodgkin's lymphoma patients had a median age of 23 (range: 7-68) years old, 64.9% had the nodular sclerosis subtype and 65% had stage III/IV disease. Nine Hodgkin's lymphoma patients (13%) and 10 (9%) non-Hodgkin lymphoma patients had some kind of cardiac toxicity. The overall survival, disease-free survival and progression-free survival in Hodgkin's lymphoma were 29%, 59% and 26%, respectively. In non-Hodgkin lymphoma, these values were 40%, 49% and 31%, respectively. High-dose cyclophosphamide-related mortality was 10% for Hodgkin's lymphoma and 5% for non-Hodgkin lymphoma patients. High-dose cyclophosphamide dosing had no impact on toxicity or survival for both groups. CONCLUSIONS: Despite a greater prevalence of poor prognostic factors, our results are comparable to the literature. The incidence of secondary neoplasias is noteworthy. Our study suggests that this approach is efficient and feasible, regardless of toxicity-related mortality.
- Published
- 2011
22. Treatment Outcome of Acute Promyelocytic Leukemia with Modified Aida Protocol
- Author
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Marcia Torresan Delamain, Gustavo De Carvalho Duarte, Katia B Pagnano, Eliana C M Miranda, Irene Lorand-Metze, and Carmino Antonio De Souza
- Subjects
Acute promyelocytic leukemia ,Pediatrics ,medicine.medical_specialty ,Mitoxantrone ,AIDA protocol ,Anthracycline ,Article Subject ,business.industry ,Treatment outcome ,Hematology ,medicine.disease ,Maintenance therapy ,Median follow-up ,Internal medicine ,medicine ,Clinical Study ,Idarubicin ,Diseases of the blood and blood-forming organs ,RC633-647.5 ,business ,medicine.drug - Abstract
We analyzed the outcome of a series of 19 newly diagnosed patients with acute promyelocytic leukemia treated with AIDA modified protocol, using mitoxantrone in place of idarubicin. Eleven patients achieved morphologic CR (58%). The remaining 8 patients had induction failure due to death during induction. Ten of eleven patients in CR achieved molecular remission after induction therapy and all the 8 patients had molecular remission after consolidation. Eight patients completed the three consolidation courses as scheduled and then proceeded to maintenance therapy. After a median follow up of 52 months, no molecular or hematological relapse has occurred. The 4-year disease-free survival is 82%. The study showed the antileukemic efficacy of mitoxantrone and that it could be used as a reasonable option in anthracycline-based strategies in APL.
- Published
- 2010
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