Application of the Central Nervous System International Prognostic Index (CNS-IPI) score in daily practice: a retrospective analysis apart from the clinical trial at two centers in Brazil.

INTRODUCTION: The diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin lymphoma (NHL) and, despite all the progress in this field, central nervous system infiltration (CNSi) still occurs at an incidence of 2-10%. The objective of the present study was to evaluate the Central Nervous System International Prognostic Index (CNS-IPI) score in daily practice regarding the reproducibility in a heterogeneous cohort apart from a clinical trial. METHODS: Primary DLBCL patients were eligible for this study, between January 2007 and January 2017. All patients were treated with rituximab-based chemotherapy, mostly R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone). The CNSi was diagnosed by liquor (positive cytology and/or immunophenotype), computerized tomography, magnetic resonance image and/or fluorodeoxy-glucose-positron emission tomography, requested only in symptomatic patients when the CNSi was clinically suspected. The CNS-IPI was assessed by graphical comparison and calibration. RESULTS: After applying the inclusion/exclusion criteria, 322 patients were available for the analysis. The median follow-up was 60 months and the median age was 58 years. Seven patients experienced CNSi, characterizing an incidence of 2.17% (7/322). Comparing groups of patients with and without CNSi, we observed that the lactate dehydrogenase (LDH), number of extranodal sites, IPI, kidney/adrenal and absence of complete response were statistically different. The CNS-IPI model stratified patients in a three-risk group model as low-, intermediate- and high-risk. In our cohort, using the same stratification, we obtained an equivalent the 2-year rate of CNS relapse of 0.0%, 0.8% and 13.8%, respectively. CONCLUSION: Our study reinforces the reproducibility of the CNS-IPI, specifically apart from clinical trials, and suggests the CNS-IPI score as a tool to guide therapy.

Characteristics and clinical outcomes of patients with ALK-positive anaplastic large cell lymphoma: Report from the prospective international T-cell lymphoma project.

The T-cell Lymphoma Project is an international registry prospective study that enrolled patients with newly diagnosed peripheral T-cell and NK-cell lymphomas (PTCL). The main objective was to define the clinical features and outcomes, establishing a robust benchmark for future clinical trials. Seventy-four institutions from 14 countries in North America, South America, Europe, and Asia collected data on patients diagnosed and treated at their respective centers between September 2006 and February 2018. Among 1553 PTCL patients, 131 (8.4% of the total cohort) were confirmed to have anaplastic large cell lymphoma - kinase positive (ALCL, ALK+). The median age of the patients was 39 years (18-84). Sixty-five patients (66%) had advanced-stage disease, although majority (45 patients, 54%) had a low-risk International Prognostic Index (IPI) score (0-1). Of 97 patients treated with chemotherapy, 97% received anthracycline-containing regimens. The overall response rate was 81%, with 69 patients (70%) achieving complete remission. Estimated OS and PFS at 3 years were 77% (95% CI: 54%-99%) and 68% (95% CI: 46%-90%), respectively, and at 5 years were very similar, 77% of OS (95% CI: 62%-92%) and 64% of PFS (95% CI: 34%-94%). Multivariate analysis for PFS showed advanced stage (hazard ratios [HR]: 4.72, 95% CI: 1.43-23.9, p = 0.015), elevated lactate dehidrogenade (LDH) (HR 4.85; 95% CI: 1.73-13.60, p = 0.001), and Eastern Cooperative Oncology Group Performance Status scale (ECOG-PS) ≥2 (HR: 5.25; 95% CI: 1.68-16.4, p = 0.024). For OS, elevated LDH (HR: 3.77; 95% CI: 1.98-14.17, p = 0.014) and ECOG-PS ≥2 (HR: 4.59; 95% CI: 1.46-14.39, p = 0.004) were identified. In summary, although the outcome of ALK+ ALCL is superior to that of other PTCLs, it remains sufficiently favorable, given the young median age of the patients. Our results confirm the usefulness of both IPI and Prognostic Index for T-cell Lymphoma (PIT) in identifying groups of patients with different outcomes. Clinical Trials ID: NCT01142674.

Diagnosis, prevention and treatment of central nervous system involvement in peripheral t-cell lymphomas.

Non-Hodgkin lymphomas with T-cell immunophenotype encompass a heterogeneous group of infrequent neoplasms that follow variable clinical courses but prevalently include aggressive behavior and high mortality rates. The involvement of the central nervous system (CNS) is an uncommon event in T-cell lymphomas, with wide variability among the different disease entities. CNS can be affected either at initial diagnosis or at recurrence, and both forms are considered "secondary CNS T-cell lymphoma". Given the low incidence of secondary CNS T-cell lymphoma, related literature is sparse, contradictory, and primarily constituted by small case series and single case reports. However, reported studies uniformly suggest high mortality rates related to this event. Therefore, to improve our ability to identify high-risk patients and offer them successful CNS prophylaxis or timely and effective treatment once the event has occurred may prevent CNS-related T-cell lymphomas deaths. For example, some entities like aggressive adult T-cell leukemia/lymphoma, extranodal natural killer/T-cell lymphoma, and other peripheral T-cell lymphomas with involvement of two or more extranodal organs are prone to CNS dissemination and should be considered for personalized CNS prophylaxis. The level of evidence suggesting an increased risk of CNS recurrence for other T-cell lymphomas and for other risk factors is lower. Published case series show that, following the example of aggressive B-cell lymphomas, patients with T-cell lymphomas and putative increased CNS risk receive different forms of prophylaxis, mostly methotrexate and cytarabine delivered by intrathecal and/or intravenous routes, with varied success. To date, achievements in the treatment of CNS involvement in patients with aggressive B-cell lymphoma were not replicated in secondary CNS T-cell lymphomas, and identification of effective therapies remains an urgent research target. This review is focused on clinical findings, diagnosis, treatment, and prognosis of patients with T-cell lymphoma experiencing CNS dissemination either at presentation or relapse. It aims to provide logical and, oftentimes, evidence-based answers to the most common questions on the most probable risk factors to CNS involvement in patients with T-cell lymphoma, the indications and strategies to prevent this life-threating event, and the management of patients with CNS disease.

Peripheral T-Cell Lymphomas: Incorporating New Developments in Diagnostics, Prognostication, and Treatment Into Clinical Practice-PART 1: PTCL-NOS, FTCL, AITL, ALCL.

Peripheral T-cell lymphomas (PTCLs) represent a heterogeneous group of diseases, with low incidence and unique epidemiology and pathobiology; they are usually clinically aggressive, with poor outcomes. There have been significant advances in our understanding of the molecular and signaling alterations seen in these malignancies. These observations have led to novel therapeutic strategies that have had a meaningful impact on outcomes. This two-part series highlights the most important aspects of PTCLs and describes current treatment options and investigative opportunities. Part 1 will cover PTCL not otherwise specified, follicular T-cell lymphoma, angioimmunoblastic T-cell lymphoma, anaplastic large-cell lymphoma (ALCL), and breast implant-associated ALCL. Part 2 will cover extranodal natural killer/T-cell lymphoma, enteropathy-associated T-cell lymphoma, indolent T-cell lymphoproliferative disorder of the gastrointestinal tract, adult T-cell leukemia/lymphoma, and hepatosplenic T-cell lymphoma.

Peripheral T-Cell Lymphomas: Incorporating New Developments in Diagnostics, Prognostication, and Treatment Into Clinical Practice-PART 2: ENKTL, EATL, Indolent T-Cell LDP of the GI Tract, ATLL, and Hepatosplenic T-Cell Lymphoma.

The World Health Organization classification for peripheral T-cell lymphomas (PTCLs) continues to evolve based on genetic and clinical distinctions of each entity. In Part 1, an overview was provided of PTCL not otherwise specified, follicular T-cell lymphoma, angioimmunoblastic T-cell lymphoma, anaplastic large cell lymphoma (ALCL), and breast implant-associated ALCL. In Part 2, this review is extended to extranodal natural killer (NK)/T-cell lymphoma, enteropathy-associated T-cell lymphoma, indolent T-cell lymphoproliferative disorder of the gastrointestinal tract, adult T-cell leukemia/lymphoma, and hepatosplenic T-cell lymphoma. Each NK/T-cell malignancy has its own signature, requiring knowledge of the appropriate diagnostic, prognostic, and therapeutic considerations when caring for afflicted individuals. Future directions will depend on discoveries that further our understanding of each disease and clinical trials that test the latest treatment options.

Transformed follicular lymphoma.

Follicular Lymphoma (FL) is the second most common type of non-Hodgkin lymphoma and is considered to be the prototype of indolent lymphomas. Histologic transformation into an aggressive lymphoma, which is expected to occur at a rate of 2 to 3% each year, is associated with rapid progression, treatment resistance, and poor prognosis. Recent modifications to the physiopathologic mechanism of transformed follicular lymphoma (t-FL) have been proposed, including genetic and epigenetic mechanisms as well as a role for the microenvironment. Although t-FL is considered a devastating complication, as it is associated with treatment-refractory disease and a dismal outcome, recent data in the rituximab era have suggested that not only is the prognosis less severe than reported in the previous literature but the risk of transformation is also lower. Thus, this study aimed to review the most recent research on t-FL in an attempt to better understand the clinical meaning of transformation from FL to diffuse large B cell lymphoma (DLBCL) and the impact of current treatment strategies on the curability of this intriguing subentity of lymphoma.

Predominance of STEMI and severity of coronary artery disease in a cohort of patients hospitalized with acute coronary syndrome: a report from ABC Medical School.

INTRODUCTION: acute coronary syndromes (ACS) represent a widely prevalent health issue with high mortality in Brazil and worldwide. The severity of ACS is not known in patients in the city of São Bernardo do Campo a municipality contiguous and adjacent to the city of São Paulo. OBJECTIVES: to study the profile of coronary disease in patients hospitalized with ACS who underwent coronary angiography in the emergency room between 2012 and 2013. METHODS: this is an observational study that included consecutive patients with ACS admitted to the emergency room of a hospital. Data collection was performed using medical records with the following variables: sex, age, risk factors for cardiovascular disease, coronary angiography. RESULTS: the sample in this period included 131 patients, of which 64.8% were men. The most prevalent diagnosis was ST-elevation myocardial infarction (STEMI) (57.2%) followed by non-ST-elevation myocardial infarction (NSTEMI) (22.1%) and unstable angina (UA) (20.6%). There were no significant differences in the epidemiology and risk factors between the diagnoses, except that heart failure was more prevalent in patients with UA. DISCUSSION: there were no differences between groups regarding the coronaries involved; however, STEMI patients showed similar numbers of multi- and singlevessel lesions, NSTEMI patients showed more multivessel lesions, and UA patients showed more multivessel lesions or lesion-free arteries. Although multivessel lesions were prevalent in all groups, STEMI patients showed a significantly higher number of single-vessel lesions compared with the other acute coronary syndromes. CONCLUSION: the study demonstrated a predominance of STEMI in the studied population, which differs from the usual results in ACS.

Predominance of STEMI and severity of coronary artery disease in a cohort of patients hospitalized with acute coronary syndrome: a report from ABC Medical School / Predomínio de infarto agudo do miocárdio com supra ST e gravidade da doença arterial coronariana em uma coorte de pacientes internados com síndrome coronariana aguda: relato da Faculdade de Medicina do ABC.

Summary Introduction: acute coronary syndromes (ACS) represent a widely prevalent health issue with high mortality in Brazil and worldwide. The severity of ACS is not known in patients in the city of São Bernardo do Campo a municipality contiguous and adjacent to the city of São Paulo. Objectives: to study the profile of coronary disease in patients hospitalized with ACS who underwent coronary angiography in the emergency room between 2012 and 2013. Methods: this is an observational study that included consecutive patients with ACS admitted to the emergency room of a hospital. Data collection was performed using medical records with the following variables: sex, age, risk factors for cardiovascular disease, coronary angiography. Results: the sample in this period included 131 patients, of which 64.8% were men. The most prevalent diagnosis was ST-elevation myocardial infarction (STEMI) (57.2%) followed by non-ST-elevation myocardial infarction (NSTEMI) (22.1%) and unstable angina (UA) (20.6%). There were no significant differences in the epidemiology and risk factors between the diagnoses, except that heart failure was more prevalent in patients with UA. Discussion: there were no differences between groups regarding the coronaries involved; however, STEMI patients showed similar numbers of multi- and singlevessel lesions, NSTEMI patients showed more multivessel lesions, and UA patients showed more multivessel lesions or lesion-free arteries. Although multivessel lesions were prevalent in all groups, STEMI patients showed a significantly higher number of single-vessel lesions compared with the other acute coronary syndromes. Conclusion: the study demonstrated a predominance of STEMI in the studied population, which differs from the usual results in ACS. .

Resumo Introdução: a síndrome coronariana aguda (SCA) é uma das principais causas de morbidade e mortalidade no Brasil e no mundo. A gravidade da coronariopatia em pacientes atendidos na cidade de São Bernardo do Campo não é conhecida. Objetivo: estudar o perfil da doença coronariana em pacientes internados com SCA e submetidos à cineangiocoronariografia entre 2012 e 2013. Métodos trata-se de estudo descritivo no qual se incluíram pacientes com SCA admitidos no setor de emergência do hospital. Houve consulta aos prontuários das seguintes variáveis: sexo, idade, fatores de risco para doença cardiovascular, diagnóstico e lesões coronárias. O erro alfa estabelecido foi de 5%. Resultados: a amostra neste período foi de 131 pacientes, sendo 64,8% homens. O diagnóstico mais prevalente foi o infarto agudo do miocárdio com supradesnível do segmento ST (IAMCST) (57,2%), seguido de infarto agudo do miocárdio sem supradesnível do segmento ST (IAMSST) (22,1%) e angina instável (AI) (20,6%). Não houve diferenças significativas quanto ao perfil epidemiológico e a fatores de risco entre os diagnósticos, com exceção da presença de insuficiência cardíaca, mais prevalente nos pacientes com AI. Discussão: as coronárias acometidas não diferiram entre os grupos; porém, enquanto o grupo IAMCST apresentou proporção de lesões multi e uniarteriais similares, o grupo IAMSST apresentou mais lesões multiarteriais, e o grupo AI, mais lesões multiarteriais ou artérias livres de lesões. Apesar das lesões multiarteriais serem prevalentes em todos os grupos, os pacientes com IAMCST apresentaram um número significativamente maior de lesões uniarteriais em comparação a pacientes com outras síndromes coronárias agudas. Conclusão: o estudo demonstrou um predomínio de IAMCST na população estudada, o que difere dos resultados habituais na SCA. .

Comparison of whole-body diffusion-weighted magnetic resonance and FDG-PET/CT in the assessment of Hodgkin's lymphoma for staging and treatment response.

Computed tomography (CT), 18F-fluorodeoxyglucose positron emission tomography (FDG-PET), and hybrid FDG-PET/CT are the most commonly used diagnostic tools for the initial staging and treatment response assessment of lymphomas [1]. The aim of this report is to compare the correlations between functional imaging markers derived from FDG-PET/CT and whole-body, diffusion-weighted magnetic resonance imaging (DW-MRI) in a young patient affected by Hodgkin's lymphoma (HL).

Acute lymphocitic leukaemia and AIDS.

Patients with AIDS have become more and more prevalent. Therefore, the onset of diseases that coexist with this condition must be studied in order to establish proper diagnosis and treatment. We report a case of a patient who reported with loss of strength in the lower limbs and a progressive worsening in his clinical picture. He was diagnosed with acute lymphocytic leukaemia, an unusual form of association with the AIDS condition. Despite the diagnosis, he evolved into pulmonary sepsis and so staging and chemotherapy treatment could not be performed.

Fever of unknown origin and the role of Plasmodium vivax in Sao Paulo.

Malaria is a disease that hits the northern part of Brazil in an endemic form. Recorded cases outside this region are unusual and, in most cases, limited to travellers. The southeast of Brazil has an extensive wilderness area with a type of vegetation similar to the one found in the equatorial rainforest. We present the case of a patient living in the southeast, with no reported travel history, who evolved to periodic fever, associated with myalgia and chills. With the positive test result for Plasmodium, the treatment for malaria was started. This case enabled the study in the Anopheles mosquito affected area, where the patient reported infection, outside the Amazon region.