ABSTRACT
Objective: To report the outcomes of a systematic literature review of guidelines and consensus on the management of paroxysmal nocturnal hemoglobinuria (PNH) and describe the main therapeutic options available worldwide. Methods: A systematic literature review was conducted in April 2018 with no time limit and reported in line with the PRISMA statement. The AGREE II instrument was used to determine the quality of each guideline included in the systematic review. Results: Eight guidelines/consensus were eligible, one developed by an international group, two in Spain, and one each in Turkey, Germany, Argentina, Australia and the United Kingdom. Supportive treatment with erythrocyte transfusion, anticoagulants and steroids is indicated by all guidelines and consensus. The use of erythropoietin is suggested by three of them. Recommendations for the prescription of eculizumab were consistent in all but one guideline, published in 2005. Allogeneic hematopoietic stem cell transplantation is reported as the only potentially curative treatment for PNH, although its association with high mortality and morbidity rates is emphasized, being indicated for a selected group of patients. The AGREE II scores applied for each domain showed in general a low and heterogeneous methodological quality among guidelines. Conclusion: Despite the low and heterogeneous methodological quality, in general the comparison of guidelines and consensus for PNH management showed consistent recommendations regarding supportive care, eculizumab and hematopoietic stem cell transplantation.
Objetivo: Relatar os desfechos de uma revisão sistemática da literatura de diretrizes e documentos de consenso sobre o manejo da hemoglobinúria paroxística noturna (HPN) e descrever as principais opções terapêuticas disponíveis mundialmente. Métodos: Uma revisão sistemática da literatura foi conduzida em abril de 2018 sem limite temporal e realizada de acordo com a recomendação PRISMA. O instrumento AGREE II foi utilizado para determinar a qualidade de cada diretriz incluída na revisão. Resultados: Foram elegíveis oito diretrizes/consensos, um desenvolvido por um grupo internacional, dois na Espanha e um em cada um dos países a seguir: Turquia, Alemanha, Argentina, Austrália e Reino Unido. O tratamento de suporte com transfusão de eritrócitos, anticoagulantes e esteroides é indicado por todos os documentos. A eritropoetina é indicada por três deles. A recomendação de prescrição do eculizumabe foi consistente em todos, exceto em um publicado em 2005. O transplante alogênico de células-tronco hematopoéticas é reportado como o único tratamento com potencial curativo para a HPN, apesar de uma enfática associação com maiores taxas de mortalidade e morbidade, sendo indicado para grupos selecionados de pacientes. Os escores AGREE II aplicados para cada domínio demonstraram, em geral, qualidade metodológica baixa e heterogênea entre as diretrizes. Conclusão: Apesar da qualidade metodológica baixa e heterogênea, em geral, a comparação de diretrizes e consensos para o manejo da HPN demonstrou recomendações consistentes quanto ao uso de tratamento de suporte, eculizumabe e transplante alogênico de células-tronco hematopoiéticas.
Subject(s)
Hematopoietic Stem Cell Transplantation , Systematic Review , Hemoglobinuria, ParoxysmalABSTRACT
Prognostic stratification in acute myeloid leukemia (AML) relies, mostly, on cytogenetics and molecular features of leukemic blasts. The LeukemiaNet prognostic scoring system has been proposed as a standardized way of evaluating prognosis in AML. We have analysed outcomes in 65 AML cases (median age of 54 years, range 18-82) treated at five hematology centers in Brazil stritified according to the European Leukemia Net (ELN) recommendations for cytogenetic and molecular analysis. We classified patients as favorable (N = 13), intermediate-1 (N = 25), intermediate-2 (N = 15), or adverse risk (N = 9). Bone marrow transplantation (BMT) was performed in 13 patients (21%). Median follow-up was 12 months. The median overall survival (OS) for all patients was 12.4 months. Median OS was 19.8, 12.4, 10.1, and 10.4 months (p = 0.24) for patients in the favorable, intermediate-1, intermediate-2, and adverse groups, respectively. Among patients receiving BMT, median OS was 26.8 months. The ELN is a valuable tool for prognostic stratification of AML patients treated in Brazil. Nevertheless, its usefulness is limited when compared to data from developed countries.
Subject(s)
Leukemia, Myeloid, Acute/mortality , Leukemia, Myeloid, Acute/therapy , Adolescent , Adult , Aged , Aged, 80 and over , Bone Marrow Transplantation/mortality , Bone Marrow Transplantation/trends , Brazil/epidemiology , Cross-Sectional Studies , Europe , Female , Humans , Leukemia, Myeloid, Acute/diagnosis , Male , Middle Aged , Prognosis , Research Design/trends , Survival Rate/trends , Treatment Outcome , Young AdultSubject(s)
Budd-Chiari Syndrome/genetics , Endothelial Cells/metabolism , Granulocytes/metabolism , Janus Kinase 2/genetics , Mutation , Alleles , Amino Acid Substitution , Budd-Chiari Syndrome/complications , Budd-Chiari Syndrome/diagnosis , Gene Frequency , Genotype , Humans , Myeloproliferative Disorders/complications , Myeloproliferative Disorders/genetics , Exome SequencingSubject(s)
Cell Cycle Proteins , Cytoplasm , Leukemia, Myeloid, Acute , Microtubule-Associated Proteins , Nuclear Proteins , Oncogene Proteins, Fusion , Aged , Cell Cycle Proteins/genetics , Cell Cycle Proteins/metabolism , Cytoplasm/genetics , Cytoplasm/metabolism , Cytoplasm/pathology , Female , Humans , Leukemia, Myeloid, Acute/genetics , Leukemia, Myeloid, Acute/metabolism , Leukemia, Myeloid, Acute/pathology , Male , Microtubule-Associated Proteins/genetics , Microtubule-Associated Proteins/metabolism , Middle Aged , Nuclear Proteins/genetics , Nuclear Proteins/metabolism , Nucleophosmin , Oncogene Proteins, Fusion/genetics , Oncogene Proteins, Fusion/metabolismABSTRACT
The ETV6 gene encodes an ETS family transcription factor that is involved in a myriad of chromosomal rearrangements found in hematological malignancies and other neoplasms. A recurrent ETV6 translocation, previously described in patients with acute myeloid leukemia (AML) (Genes Chromosomes Cancer 51:328-337,2012, Leuk Res 35:e212-214, 2011), whose partner has not been identified is t(7;12)(p15;p13). We herein report that the t(7;12)(p15;p13) fuses ETV6 to ANLN, a gene not previously implicated in the pathogenesis of hematological malignancies, and we demonstrate that this translocation leads to high expression of the fusion transcript in the myeloid and lymphoid lineages.
Subject(s)
Leukemia, Myeloid, Acute/metabolism , Microfilament Proteins/metabolism , Proto-Oncogene Proteins c-ets/metabolism , Repressor Proteins/metabolism , Adult , Female , Humans , Leukemia, Myeloid, Acute/genetics , Microfilament Proteins/genetics , Oncogene Proteins, Fusion/genetics , Oncogene Proteins, Fusion/metabolism , Proto-Oncogene Proteins c-ets/genetics , Repressor Proteins/genetics , Transcription Factors , ETS Translocation Variant 6 ProteinSubject(s)
Blood Platelets/immunology , Isoantibodies/immunology , Myeloablative Agonists/administration & dosage , Peripheral Blood Stem Cell Transplantation , Transplantation Conditioning , Unrelated Donors , Aged , Allografts , Antibody Specificity/drug effects , Antibody Specificity/immunology , Female , HLA Antigens , Humans , MaleABSTRACT
Objective: To identify the incidence of alloimmunization in sickle cell disease patients, as well as autoantibodies and the phenotypic profile of these patients for the following erythrocyte antigen groups: Rh, Kell, Kidd, Duffy and MNS. Methods: fifty-seven patients were evaluated during follow-up at the Anemia Outpatient Clinic of Irmandade da Santa Casa de São Paulo, where a search for irregular antibodies and phenotyping was carried out. Results: Patients' median alloimmunization age in sickle cell disease was 25 years, and irregular antibodies were found in 22.6% of them. Anti-Kell antibody was the most frequent (7.5%) followed by anti-C (5.7%). Conclusion: The prevalence of alloimmunization and of patients with autoantibodies among individuals with sickle cell disease followed at the Anemia Outpatient Clinic of Irmandade da Santa Casa de Misericórdia de São de Paulo was determined. The risk of alloimmunization was higher in patients who received more than 3 red blood cell units in the past 2 years. The most prevalent alloantibodies were anti-Kell and anti-C.
Objetivo: Identificar a incidência de aloimunização em pacientes com doença falciforme, a incidência de autoanticorpos e o perfil fenotípico dos pacientes para os seguintes grupos de antígenos eritrocitários: Rh, Kell, Kidd, Duffy e MNS. Métodos: Foram avaliados 57 pacientes em acompanhamento no Ambulatório de Anemias da Irmandade da Santa Casa de São Paulo, sendo realizada a pesquisa de anticorpos irregulares e a fenotipagem eritrocitária. Resultados: A mediana de idade foi de 25 anos, sendo que 22,6% dos pacientes apresentavam anticorpos irregulares. O anticorpo anti-Kell foi o mais frequente (7,5%), seguido de anti-C (5,7%). Conclusão: Foi determinada a prevalência de aloimunização e de pacientes com autoanticorpos em indivíduos com anemia falciforme seguidos no Ambulatório de Anemias da Irmandade da Santa Casa de Misericórdia de São de Paulo. O risco de aloimunização foi maior em pacientes que receberam mais do que 3 unidades de hemácias nos últimos 2 anos. Os aloanticorpos mais prevalentes foram anti-Kell e anti-C.
Subject(s)
Humans , Male , Female , Anemia, Sickle Cell , Autoantibodies , Blood Group Antigens , Blood TransfusionABSTRACT
Objective: To identify how the Brazilian hematology centers treated and diagnosed cases of acute myeloid leukemia in 2009. Methods: An epidemiological observational multicenter study of 11 listed Brazilian centers that treat acute myeloid leukemia and perform bone marrow transplantation. Data were collected from clinical charts of patients with acute myeloid leukemia treated at the said centers between 2005 and 2009. The availability for immunophenotyping and cytogenetic tests was assessed. Results:During 2009, a total of 345 new cases of acute myeloid leukemia were diagnosed. Differences were noted in the tests performed between patients who initiated treatment at the center and those referred for treatment. Of the participating centers, 72% conducted some type of molecular study in acute myeloid leukemia upon diagnosis. Conclusion: Treatment for acute myeloid leukemia in Brazil shows significantly inferior results when compared to other centers worldwide.
Objetivo: Identificar como centros de hematologia brasileiros trataram e diagnosticaram os casos de leucemia mieloide aguda no ano de 2009. Métodos: Estudo epidemiológico, observacional, multicêntrico de 11 centros brasileiros cadastrados para tratamento de leucemia mieloide aguda e transplante de medula óssea. Os dados foram coletados a partir de prontuários de pacientes com leucemia mieloide aguda tratados nos centros citados entre os anos de 2005 e 2009. Foi avaliada a disponibilidade para realização de exames de imunofenotipagem e citogenética nos centros estudados. Resultados: Foram diagnosticados 345 casos novos de leucemia mieloide aguda no ano de 2009. Observaram-se diferenças na realização de exames entre pacientes que iniciaram o tratamento no centro em relação àqueles referenciados para tratamento. Dos centros participantes, 72% realizaram algum tipo de pesquisa molecular em leucemia mieloide aguda ao diagnóstico. Conclusão: O tratamento da leucemia mieloide aguda no Brasil apresenta resultados muito inferiores quando comparado a outros centros mundiais.
Subject(s)
Humans , Male , Female , Cytogenetic Analysis , Leukemia, Myeloid, Acute , Molecular Diagnostic Techniques , TherapeuticsABSTRACT
Objective: To analyze the outcome of patients treated with gemtuzumab ozogamycin combined with conventional therapy treated at Hospital Israelita Albert Einstein. Methods: 14 patients who had high risk features (secondary leukemia, unfavorable cytogenetics, and refractory disease) were treated with gemtuzumab ozogamycincombined with conventional therapy and their outcome was analysed by reviewing their medical records. Results: Overall response rate was 58%, with 43% achieving complete response, with a median followup of 11 months, event-free survival was 3 months. Eleven patients died, 6 of them due to refractory acute myeloid leukemia. Only four patients presented with grade 3 to 4 toxicities and only one patient had sinusoidal obstruction syndrome after bone marrow transplant. Conclusion: gemtuzumab ozogamycin combined with chemotherapy is a feasible treatment regimen in acute myeloid leukemia patients. However, further studies are necessary to clarify which subgroup of patients may benefit from this treatment.
Objetivo: Analisar a evolução de pacientes tratados com gemtuzumabe ozogamicina combinado à terapêutica convencional no Hospital Israelita Albert Einstein. Métodos: 14 pacientes que tinham alto risco (leucemia secundária, citogenética desfavorávele doença refratária) foram tratados com gentuzumabe ozogamicina associado à terapêutica convencional, e sua evolução foi analisada por meio de seus prontuários médicos. Resultados: A taxa total de resposta foi de 58%, com 43% chegando a resposta completa, em acompanhamento médio de 11 meses, e três meses com intervalo de sobrevivência livre. Foram a óbito 11 pacientes, 6 deles por leucemia mieloide aguda. Somente quatro pacientes apresentaram graus 3 a 4 de toxicidade e apenas um paciente teve síndrome de obstrução sinusoidal após transplante de medula. Conclusão: Gemtuzumabe ozogamicina associado à terapêutica quimioterápica convencional éum tratamento factível em pacientes com leucemia mieloide aguda. Contudo, novos estudos são necessários para esclarecer qual o subgrupo de pacientes que pode se beneficiar desse tratamento.
Subject(s)
Humans , Male , Female , Aged , Antineoplastic Agents/therapeutic use , Leukemia, Myeloid, Acute/drug therapy , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , RadiotherapyABSTRACT
Mucosa-associated lymphoid tissue (MALT) is the most common extranodal lymphoma, with one third of the cases occurring in the stomach. Surgical treatment is a possible option. This case report describes an obese woman (body mass index 46 kg/m2) seeking bariatric surgery, with elevated serum cholesterol and uric acid, negative for Helicobacter pylori but with a positive biopsy for MALT (immunohistochemistry), stage IA. She was submitted to a Roux-en-Y gastric bypass and gastric resection. Two months later, she had lost 20 kg and the MALT lymphoma was in complete remission.
Subject(s)
Gastrectomy , Gastric Bypass , Lymphoma, B-Cell, Marginal Zone/epidemiology , Lymphoma, B-Cell, Marginal Zone/surgery , Obesity, Morbid/epidemiology , Obesity, Morbid/surgery , Stomach Neoplasms/epidemiology , Stomach Neoplasms/surgery , Adult , Female , HumansABSTRACT
OBJECTIVE: To identify the incidence of alloimmunization in sickle cell disease patients, as well as autoantibodies and the phenotypic profile of these patients for the following erythrocyte antigen groups: Rh, Kell, Kidd, Duffy and MNS. METHODS: fifty-seven patients were evaluated during follow-up at the Anemia Outpatient Clinic of Irmandade da Santa Casa de São Paulo, where a search for irregular antibodies and phenotyping was carried out. RESULTS: Patients' median alloimmunization age in sickle cell disease was 25 years, and irregular antibodies were found in 22.6% of them. Anti-Kell antibody was the most frequent (7.5%) followed by anti-C (5.7%). CONCLUSION: The prevalence of alloimmunization and of patients with autoantibodies among individuals with sickle cell disease followed at the Anemia Outpatient Clinic of Irmandade da Santa Casa de Misericórdia de São de Paulo was determined. The risk of alloimmunization was higher in patients who received more than 3 red blood cell units in the past 2 years. The most prevalent alloantibodies were anti-Kell and anti-C.
ABSTRACT
OBJECTIVE: To identify how the Brazilian hematology centers treated and diagnosed cases of acute myeloid leukemia in 2009. METHODS: An epidemiological observational multicenter study of 11 listed Brazilian centers that treat acute myeloid leukemia and perform bone marrow transplantation. Data were collected from clinical charts of patients with acute myeloid leukemia treated at the said centers between 2005 and 2009. The availability for immunophenotyping and cytogenetic tests was assessed. RESULTS: During 2009, a total of 345 new cases of acute myeloid leukemia were diagnosed. Differences were noted in the tests performed between patients who initiated treatment at the center and those referred for treatment. Of the participating centers, 72% conducted some type of molecular study in acute myeloid leukemia upon diagnosis. CONCLUSION: Treatment for acute myeloid leukemia in Brazil shows significantly inferior results when compared to other centers worldwide.
ABSTRACT
OBJECTIVE: To analyze the outcome of patients treated with gemtuzumab ozogamycin combined with conventional therapy treated at Hospital Israelita Albert Einstein. METHODS: 14 patients who had high risk features (secondary leukemia, unfavorable cytogenetics, and refractory disease) were treated with gemtuzumab ozogamycin combined with conventional therapy and their outcome was analysed by reviewing their medical records. RESULTS: Overall response rate was 58%, with 43% achieving complete response, with a median follow-up of 11 months, event-free survival was 3 months. Eleven patients died, 6 of them due to refractory acute myeloid leukemia. Only four patients presented with grade 3 to 4 toxicities and only one patient had sinusoidal obstruction syndrome after bone marrow transplant. CONCLUSION: gemtuzumab ozogamycin combined with chemotherapy is a feasible treatment regimen in acute myeloid leukemia patients. However, further studies are necessary to clarify which subgroup of patients may beneft from this treatment.
