RESUMO: Objetivo: Atualizar achados de estudos observacionais analíticos sobre a associação entre exposição ocupacional a organofosforados e neoplasias hematológicas. Métodos: Revisão sistemática de literatura, incluindo estudos de coorte e caso controle, sem limitação de tempo de publicação, nos idiomas português e inglês. O rastreamento de artigos foi feito no período de junho de 2017 a julho de 2019 nas bases de dados PubMed, MEDLINE, LILACS, Web of Science e Scopus. A avaliação qualitativa de risco de viés foi feita com a Escala Newcastle-Otawa e com o Checklist Downs e Black. Os resultados foram apresentados segundo as recomendações da Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA). Resultados: Foram elegíveis 17 estudos avaliados como de boa/alta qualidade metodológica. A exposição a diazinon (um coorte), fonofós (um coorte), diclorvós, crotoxifós e fanfur (um caso controle) associou-se à leucemia, enquanto a exposição a organofosforados associou-se aos linfomas (seis caso controle). O risco de linfoma não-Hodgkin foi maior para os indivíduos expostos a diazinon (um caso controle) e malation (três caso controle), em relação aos não expostos. O mieloma múltiplo ocorreu mais comumente em expostos a organofosforados do que entre os não expostos (um caso controle). Conclusão: A exposição ocupacional a organofosforados aumenta o risco de neoplasias hematológicas, sobretudo entre os indivíduos com maior período de exposição. Medidas de monitoramento de trabalhadores e de controle da exposição são recomendadas.

ABSTRACT: Objective: To update findings of observational analytical studies on the association between occupational exposure to organophosphates and hematologic malignancies. Methodology: Systematic literature review, including cohort and case-control studies, without limitation of publication time, in Portuguese and English. The articles were traced from June 2017 to July 2019 in PubMed, MEDLINE, LILACS, Web of Science, and Scopus databases. The qualitative bias risk assessment was performed using the Newcastle-Ottawa Scale and the Downs and Black Checklist. Results were presented according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA). Results: Seventeen studies evaluated as good/high methodological quality were eligible. Exposure to diazinon (1 cohort), phonophos (1 cohort), dichlorvos, crotoxiphos and famphur (1 case control) was associated with leukemia, while exposure to organophosphate was associated to lymphomas (6 case control); the risk of non-Hodgkin’s lymphoma was higher in those exposed to diazinon (1 control case) and malathion (3 control case) than non-exposed ones. Multiple myeloma occurred more commonly in organophosphate exposed than in non-exposed individuals (1 case-control). Conclusion: Occupational exposure to organophosphates increases the risk of hematologic malignancies, especially among individuals with longer exposure periods. Worker monitoring and exposure control measures are recommended.

RESUMO: Objetivo: Atualizar achados de estudos observacionais analíticos sobre a associação entre exposição ocupacional a organofosforados e neoplasias hematológicas. Métodos: Revisão sistemática de literatura, incluindo estudos de coorte e caso controle, sem limitação de tempo de publicação, nos idiomas português e inglês. O rastreamento de artigos foi feito no período de junho de 2017 a julho de 2019 nas bases de dados PubMed, MEDLINE, LILACS, Web of Science e Scopus. A avaliação qualitativa de risco de viés foi feita com a Escala Newcastle-Otawa e com o Checklist Downs e Black. Os resultados foram apresentados segundo as recomendações da Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA). Resultados: Foram elegíveis 17 estudos avaliados como de boa/alta qualidade metodológica. A exposição a diazinon (um coorte), fonofós (um coorte), diclorvós, crotoxifós e fanfur (um caso controle) associou-se à leucemia, enquanto a exposição a organofosforados associou-se aos linfomas (seis caso controle). O risco de linfoma não-Hodgkin foi maior para os indivíduos expostos a diazinon (um caso controle) e malation (três caso controle), em relação aos não expostos. O mieloma múltiplo ocorreu mais comumente em expostos a organofosforados do que entre os não expostos (um caso controle). Conclusão: A exposição ocupacional a organofosforados aumenta o risco de neoplasias hematológicas, sobretudo entre os indivíduos com maior período de exposição. Medidas de monitoramento de trabalhadores e de controle da exposição são recomendadas.

ABSTRACT: Objective: To update findings of observational analytical studies on the association between occupational exposure to organophosphates and hematologic malignancies. Methodology: Systematic literature review, including cohort and case-control studies, without limitation of publication time, in Portuguese and English. The articles were traced from June 2017 to July 2019 in PubMed, MEDLINE, LILACS, Web of Science, and Scopus databases. The qualitative bias risk assessment was performed using the Newcastle-Ottawa Scale and the Downs and Black Checklist. Results were presented according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA). Results: Seventeen studies evaluated as good/high methodological quality were eligible. Exposure to diazinon (1 cohort), phonophos (1 cohort), dichlorvos, crotoxiphos and famphur (1 case control) was associated with leukemia, while exposure to organophosphate was associated to lymphomas (6 case control); the risk of non-Hodgkin’s lymphoma was higher in those exposed to diazinon (1 control case) and malathion (3 control case) than non-exposed ones. Multiple myeloma occurred more commonly in organophosphate exposed than in non-exposed individuals (1 case-control). Conclusion: Occupational exposure to organophosphates increases the risk of hematologic malignancies, especially among individuals with longer exposure periods. Worker monitoring and exposure control measures are recommended.

Abstract Background Despite all the scientific progress that has been made on understanding the disease, prognosis for patients with relapsed and refractory Hodgkin's lymphoma remains poor and the treatment is palliative in the majority of the cases. Thus, the aim of this study was to present the results on the compassionate use of everolimus in a group of patients who were monitored at nine different centers in Brazil. Methods A 10-mg oral dose of everolimus was given to each patient daily. Response time was evaluated from the beginning of medication use until loss of response, toxicity or medical decision to cease treatment. Results Thirty-three patients were evaluated. The median age at the beginning of medication administration was 29 years. Patients had received a median of five prior therapies. Overall response rate was 45.4%, with 13 patients achieving partial response, two achieved clinical response, 14 remained with stable disease, two had disease progression, and two were not evaluated. Patients received a median of 14 cycles. Progression-free survival was nine months, and overall survival was estimated to be 36 months. Three patients used the medication for more than four years. The most frequently reported adverse events were thrombocytopenia and hypercholesterolemia. Three patients had pulmonary toxicity. Grade III and IV adverse events occurred in 39% of the patients. Conclusion Everolimus was found to provide a response in a group of patients with refractory or relapsed Hodgkin's lymphoma who had adequate tolerability to the drug.

Abstract In addition to findings from conventional magnetic resonance imaging, modern magnetic resonance imaging techniques have provided important information about tumor metabolism, in vivo metabolite formation, water molecule diffusion, microvascular density, and blood-brain barrier permeability, all of which have improved the in vivo diagnostic accuracy of this method in the evaluation of primary central nervous system lymphoma. These nonconventional magnetic resonance techniques are useful in the clinical practice because they enhance conventional magnetic resonance imaging by reinforcing the possibility of a diagnosis and by allowing the early detection of disease recurrence. This report is a review of the most relevant contributions of nonconventional magnetic resonance techniques to the imaging diagnosis of primary central nervous system lymphoma, the differential diagnosis of this disease, and the prognosis of patients. This paper aims to describe a wide range of presentations of primary central nervous system lymphoma, their appearance in imaging, and the differential diagnoses of this disease.

OBJECTIVE: To demonstrate a correlation of C-reactive protein levels with disease stage and response to treatment in Hodgkin's lymphoma patients of the Hematology Service of Santa Casa de São Paulo.METHODS: A retrospective study based on review of medical records was carried out of 38 patients diagnosed with Hodgkin's lymphoma between October 2010 and December 2012. Three patients met the exclusion criteria, giving a final sample of 35 patients for analysis. C-reactive protein levels >1 mg/dL were considered positive.RESULTS: Among the patients analyzed, median age was 29 years, 65% were male and 85% had the classical nodular sclerosis subtype. Twenty-nine (82%) were in the advanced stage and 28% had bulky mass at diagnosis. Seventeen percent had bone marrow invasion by lymphoma. Baseline C-reactive protein levels were associated with both stage (p-value = 0.0035) and presence or absence of B symptoms (p-value = 0.008). The highest C-reactive protein levels were detected in patients with advanced disease while no patients with localized disease had C-reactive protein >5 mg/dL (p-value = 0.02). After the first treatment cycle, C-reactive protein fell to near-normal levels and no direct association with response pattern was found. As the mean follow-up was only 14 months, it was not possible to determine whether relapse was accompanied by a further increase in C-reactive protein.CONCLUSION: Baseline C-reactive protein levels directly correlated with stage and presence or absence of B symptoms, but the degree of improvement with treatment did not correlate with response pattern. After a longer follow-up, it may be possible to assess whether relapse correlates with a further increase in C-reactive protein levels.

OBJECTIVE: To investigate the incidence and risk factors of infiltration of the central nervous system after the initial treatment of diffuse large B-cell lymphoma in patients treated at Santa Casa de Misericórdia de São Paulo. METHODS: A total of 133 patients treated for diffuse large B-cell lymphoma from January 2001 to April 2008 were retrospectively analyzed in respect to the incidence and risk factors of secondary central nervous system involvement of lymphoma. Intrathecal prophylaxis was not a standard procedure for patients considered to be at risk. This analysis includes patients whether they received rituximab as first-line treatment or not. RESULTS: Nine of 133 (6.7%) patients developed central nervous system disease after a mean observation time of 29 months. The median time to relapse or progression was 7.9 months after diagnosis and all but one patient died despite the treatment administered. Twenty-six (19.5%) patients of this cohort received rituximab as first-line treatment and nine (7.1%) received intrathecal chemoprophylaxis. Of the nine patients that relapsed, seven (77.7%) had parenchymal central nervous system involvement; seven (77.7%) had stage III or IV disease; one (11.1%) had bone marrow involvement; two (22.2%) had received intrathecal chemoprophylaxis; and 3 (33.3%) had taken rituximab. In a multivariate analysis, the risk factors for this infiltration were being male, previous use of intrathecal chemotherapy and patients that were refractory to initial treatment. CONCLUSION: Central nervous system infiltration in this cohort is similar to that of previous reports in the literature. As this was a small cohort with a rare event, only three risk factors were important for this infiltration