Rituximab, gemcitabine and oxaliplatin in relapsed or refractory indolent and mantle cell lymphoma: results of a multicenter phase I/II-study of the German Low Grade Lymphoma Study Group.

Rituximab, gemcitabine and oxaliplatin (R-GemOx) has demonstrated to be effective and safe in lymphoma patients. We aimed to determine the maximum tolerated dose (MTD) of oxaliplatin in combination with rituximab and gemcitabine and to explore the efficacy and safety of R-GemOx in relapsed or refractory (r/r) indolent and mantle cell lymphoma (MCL). In this single-arm, phase I/II trial, we enrolled 55 patients with r/r indolent lymphoma and MCL not suitable for autologous stem-cell transplantation. Patients received 4 cycles of R-GemOx. In the dose escalation group, 70 mg/m2 of oxaliplatin was applied and interindividually increased by 10 mg/m2 until the MTD was reached together with fixed doses of rituximab and gemcitabine. At the oxaliplatin MTD, an extension cohort was opened. Primary aim was to detect an overall response rate (ORR) greater than 65% (α = 0.05). Oxaliplatin 70 mg/m2 (MTD) was chosen for the extension cohort after 3 of 6 patients experienced a DLT at 80 mg/m2. Among 46 patients evaluable for the efficacy analysis ORR was 72% (33/46), missing the primary aim of the study (p = 0.21). After a median follow-up of 7.9 years, median PFS and OS were 1.0 and 2.1 years. Most frequent grade ≥ 3 adverse events were cytopenias. R-GemOx induces decent response rates in r/r indolent lymphoma and MCL, though novel targeted therapies have largely replaced chemotherapy in the relapse setting. Particularly in MCL, R-GemOx might be an alternative option in late relapses or as bridging to CAR-T-cells. This study was registered with ClinicalTrials.gov on Aug 4th, 2009, number NCT00954005.

Phytosterol supplementation in the treatment of dyslipidemia in children and adolescents: a systematic review / Suplementação de fitoesteróis no tratamento da dislipidemia em crianças e adolescentes: uma revisão sistemática

ABSTRACT Objective: To carry out a systematic review on the effects of phytosterol supplementation on the treatment of dyslipidemia in children and adolescents. Data sources: Review in the SciELO, Lilacs, Bireme, PubMed and Web of Science databases, with no time limit. Descriptors: phytosterols or plant sterols and dyslipidemias, hypercholesterolemia, cholesterol, children, adolescent, in English and Portuguese. The articles included were published in Portuguese, English or Spanish and evaluated the effect of phytosterol supplementation in pediatric patients with dyslipidemia. Documents that involved adults or animals, review papers, case studies and abstracts were excluded. Two authors performed independent extraction of articles. Of 113 abstracts, 19 were read in full and 12 were used in this manuscript. Data synthesis: Phytosterol supplementation to reduce cholesterol levels has been shown to be effective in reducing LDL-cholesterol levels by approximately 10%, with reductions above 10% in LDL-cholesterol levels observed after 8 to 12 weeks of intervention. Studies have not shown significant changes in HDL-cholesterol and triglyceride levels. Based on the absence of adverse effects, its use seems to be safe and of good tolerance in children and adolescents. Conclusions: Phytosterol supplementation seems to be of great therapeutic aid for the treatment of hypercholesterolemia in children and adolescents. Further studies assessing the long-term effect of phytosterol supplementation are necessary.

RESUMO Objetivo: Realizar uma revisão sistemática sobre os efeitos da suplementação de fitoesteróis no tratamento da dislipidemia em crianças e adolescentes. Fontes de dados: Revisão nos bancos SciELO, Lilacs, Bireme, Pubmed e Web of Science, sem limite de tempo. Descritores: phytosterols or plant sterols, dyslipidemias, hypercholesterolemia, cholesterol, children, adolescent, nas línguas inglesa e portuguesa. Os artigos incluídos foram publicados nos idiomas português, inglês ou espanhol e avaliaram o efeito da suplementação de fitoesteróis em pacientes pediátricos com dislipidemia. Estudos que envolviam adultos ou animais, trabalhos de revisão, estudos de caso e resumos foram excluídos. A extração independente de artigos foi realizada por dois autores. Do total de 113 resumos, 19 foram lidos na íntegra, e 12 utilizados neste manuscrito. Síntese de dados: A suplementação de fitoesteróis para a redução dos níveis de colesterol mostrou-se eficiente, de forma a promover a redução de aproximadamente 10% dos níveis de LDL-colesterol, sendo observadas reduções acima de 10% em 8 a 12 semanas de intervenção. Os estudos não mostraram alterações significantes nos níveis de HDL-colesterol e triglicérides. Com base na ausência de efeitos adversos, seu uso parece ser seguro e de boa tolerância em crianças e adolescentes. Conclusões: A suplementação com fitoesteróis parece ser de grande auxílio terapêutico para o tratamento da hipercolesterolemia em crianças e adolescentes. São necessários mais estudos que avaliem o efeito em longo prazo da suplementação de fitoesteróis.

Phytosterol supplementation in the treatment of dyslipidemia in children and adolescents: a systematic review.

OBJECTIVE: To carry out a systematic review on the effects of phytosterol supplementation on the treatment of dyslipidemia in children and adolescents. DATA SOURCES: Review in the SciELO, Lilacs, Bireme, PubMed and Web of Science databases, with no time limit. Descriptors: phytosterols or plant sterols and dyslipidemias, hypercholesterolemia, cholesterol, children, adolescent, in English and Portuguese. The articles included were published in Portuguese, English or Spanish and evaluated the effect of phytosterol supplementation in pediatric patients with dyslipidemia. Documents that involved adults or animals, review papers, case studies and abstracts were excluded. Two authors performed independent extraction of articles. Of 113 abstracts, 19 were read in full and 12 were used in this manuscript. DATA SYNTHESIS: Phytosterol supplementation to reduce cholesterol levels has been shown to be effective in reducing LDL-cholesterol levels by approximately 10%, with reductions above 10% in LDL-cholesterol levels observed after 8 to 12 weeks of intervention. Studies have not shown significant changes in HDL-cholesterol and triglyceride levels. Based on the absence of adverse effects, its use seems to be safe and of good tolerance in children and adolescents. CONCLUSIONS: Phytosterol supplementation seems to be of great therapeutic aid for the treatment of hypercholesterolemia in children and adolescents. Further studies assessing the long-term effect of phytosterol supplementation are necessary.

The performance of three oncogeriatric screening tools - G8, optimised G8 and CARG - in predicting chemotherapy-related toxicity in older patients with cancer. A prospective clinical study.

BACKGROUND: Older patients are vulnerable to chemotherapy-related toxicity (CRT). Therefore we evaluated screening tools in their power to predict CRT. METHODS: Patients with cancer aged ≥65 years completed three screening questionnaires (G8, optimised G8 and Cancer and Ageing Research Group (CARG). Additionally, Comprehensive geriatric assessment (CGA) for verification of supportive care needs was undertaken on patients with impaired G8 scores. During chemotherapy treatment patients were assessed, capturing grade 0-5 CRT as defined by NCI CTCAE 4. RESULTS: 104 patients with non-haematological cancers were included at three study sites. Median age was 73 years (range 65-85). Onco-geriatric screening detected 74% as impaired using G8 and optimised G8 questionnaires and 86% using CARG screening. Grade 3-5 toxicity affected 64.4% of all patients. G8 (OR 0.3 95% CI [0.1;1.0]) and optimised G8 (OR 0.4 95% CI [0.1; 1.5]) did not reliably predict CRT, whereas screening with CARG demonstrated a strong prediction of severe CRT: OR 4.2, 95% CI [1.1, 15.9]. CGA was undertaken on 66 patients, revealing deficiencies in nutritional (83%) and functional-status (54%) and occurrence of relevant comorbidity (53%). CONCLUSION: The CARG tool could be useful for predicting CRT. CGA showed clinically relevant supportive care needs in patients with a positive G8 screening.

Associação entre estado nutricional e vulnerabilidade em idosos institucionalizados / Association between nutritional status and vulnerability in institutionalized elderly

Objetivo: Associar o estado nutricional e a vulnerabilidade em idosos institucionalizados da capital e do interior do Estado de São Paulo. Método: Trata-se de um estudo transversal descritivo, realizado em três Instituições de Longa Permanência para Idosos (ILPIs) da capital e do interior de São Paulo, cuja amostra foi composta por 52 idosos. Foram aplicados a Mini Avaliação Nutricional (MAN) e o Protocolo de Identificação do Idoso Vulnerável (VES-13), e coletadas variáveis antropométricas para caracterizar o risco nutricional e a vulnerabilidade dos idosos. As análises estatísticas foram realizadas com auxílio do software SPSS, em um nível de significância de 5%. Resultados: A idade média dos participantes foi de 76,23 anos (DP=9,18), sendo que os idosos da capital eram mais velhos, com idade média de 81,23 anos (p<0,001). Somente os idosos do interior não apresentavam risco nutricional (p<0,001). Os idosos do interior apresentaram média de circunferência da panturrilha maior do que os idosos da capital (p<0,001). Os idosos da capital eram significativamente mais vulneráveis do que os do interior (p<0,001; 92,3% vs. 42,3%). Houve correlação moderada e inversa entre MAN e VES-13 (r=0,55; p<0,01). Embora os idosos da capital fossem significativamente mais velhos, não se observou influência significativa da idade na vulnerabilidade dos idosos. Conclusões: Os idosos institucionalizados do interior apresentaram melhor estado nutricional, menor risco nutricional e menor vulnerabilidade em comparação aos idosos da capital paulista.

Primary high-grade non-Hodgkin lymphoma of the trachea in an adolescent.

Lymphomas belong to the most treatable and curable malignant tumors of childhood. They should always be considered among differential diagnosis, even in unusual locations, and tumor material should be processed adequately to reach true diagnosis. The authors report on a 16-year-old adolescent with a tracheal lymphoma, a rare location of lymphoma in childhood. Because only formalin-fixed tumor material was obtained, pathology showed two differential diagnoses and the entity could never be fully clarified as anaplastic plasmacytoma or plasmoblastic lymphoma. Thus, full lymphoma diagnostic workup should be performed even in tumors with atypical location.

Randomized study to evaluate the use of high-dose therapy as part of primary treatment for "aggressive" lymphoma.

PURPOSE: This trial of the German High-Grade Non-Hodgkin's Lymphoma Study Group compares the use of high-dose therapy (HDT) as part of primary treatment with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) plus etoposide followed by involved-field (IF) radiotherapy in a randomized, multicenter, phase III study. PATIENTS AND METHODS: Three hundred twelve patients with "aggressive" non-Hodgkin's lymphoma aged

Intermediate-dose cytarabine treatment delivered at moderate infusion rates for de novo acute myeloid leukemia-results of a phase I-II study.

Published randomized trials on different cytarabine doses for the treatment of acute myeloid leukemia (AML) provide evidence of a dose-response effect. However, high-dose cytarabine (HIDAC) regimens correlate with increased morbidity and toxicity related mortality. Typical HIDAC regimens deliver 6 g/m2/d in infusion rates of 500-3000 mg/m2/h. However, pharmacokinetic measurements indicate that intracellular Ara-CTP formation is saturated at lower infusion rates than used in HIDAC schedules, probably causing cytarabine accumulation in the plasma and increased toxicity. It was our objective to investigate in a prospective non-randomized phase I-II study feasibility and efficacy of intermediate doses of cytarabine delivered at the presumptive saturating moderate infusion rate (mir-IDAC), as induction therapy in order to optimize intensified treatment for acute myeloid leukemia. Forty previously untreated patients younger than 60 years of age with de novo AML received intermediate doses of cytarabine (2-4 g/m2/d) at moderate infusion rates (250-667 mg/m2/h) over 6 or 8 h. Cytarabine was applied on alternate days (day 1, 3, 5, 7) in combination with an anthracycline as induction and consolidation therapy. Thirty-two of the 40 patients (80%, 95%CI:64-91%) achieved CR after induction treatment. Treatment-related mortality during induction chemotherapy was 2.5%. No cerebellar toxicity was observed. After two to four mir-IDAC courses stem cell harvesting was successful in 71% of the patients eligible for high-dose chemotherapy. After three years 56% (95%CI:40-72%) of all patients are alive and 59% (95%CI:42-76%) of the patients who entered CR are free of leukemia. In conclusion, favorable long-term outcomes and moderate acute toxicities were observed in patients with de novo AML treated with IDAC schedules delivered at moderate infusion rates (mir-IDAC) starting as induction treatment. The data suggest that a randomized trial should now be undertaken to examine whether mir-IDAC has clinical advantages over HIDAC.