Current perspectives on the management of refractory or relapsed classic hodgkin lymphoma in brazil: Balancing efficacy, safety, and tolerability.

Classic Hodgkin lymphoma (CHL), which accounts for 90-95% of all cases of Hodgkin lymphoma, is the most frequent cancer in adolescents and the most frequent lymphoma in adolescents and young adults. Despite progressive improvements over past decades and the general sensitivity of CHL to frontline chemotherapy, approximately 10-15% of patients have refractory disease that either does not respond to such therapy or progresses after an initial partial response. In patients with refractory or relapsed disease, standard treatment until recently consisted mainly of salvage chemotherapy, in many cases followed by high-dose chemotherapy and autologous stem-cell transplantation. However, improved understanding of the pathobiology of CHL, coupled with the introduction of novel agents, has markedly changed the treatment landscape in the past decade. Although refractory or relapsed CHL continues to be challenging, the therapeutic landscape is undergoing profound changes brought about by novel agents, particularly brentuximab vedotin and immunotherapy. In this review, we discuss the most salient treatment options for adult patients with refractory or relapsed CHL, with a special focus on the Brazilian healthcare setting, which is constrained by inherent characteristics of this system. In the attempt to balance efficacy, safety and tolerability, practicing physicians must rely on clinical trials and on results from real-world studies, and use their own point of view and experience, as well as patient characteristics and previous therapy, to make treatment decisions for refractory or relapsed CHL.

Circulating extracellular vesicles as a predictive biomarker for acute graft-versus-host disease.

The diagnosis and management of graft-versus-host disease (GVHD) have remained important challenges in allogeneic stem cell transplantation (allo-SCT). Novel diagnostic methods and therapeutic interventions are needed to further improve on patient outcomes. Extracellular vesicles (EV) are microvesicles formed by the inversion of the phospholipid bilayer of different cellular subtypes and have been described as biomarkers of cellular damage, activation, and intercellular signaling in numerous clinical scenarios. We studied the association between the levels of EV and the incidence of acute GVHD (aGVHD). Forty patients undergoing allo-SCT for hematological malignancies had their plasma collected at neutrophil engraftment. Using flow cytometry combined with fluorescent beads, the total circulating EV count (TEV) was established with annexin V positivity; CD61 positivity was used for platelet-derived EV (PEV), and CD235 positivity, for erythrocyte-derived EV (EryEV). TEV counts greater than 516/µL were associated with a higher cumulative incidence (CI) of grade II to IV aGVHD (54% vs. 21%; p = 0.02), as were EryEV counts above 357 /µL (CI of aGVHD: 59% vs. 26%; p = 0.04). In patients who are exposed to reduced intensity conditioning (RIC), stronger associations of both high TEV and EryEV counts with aGVHD were observed (77% vs. 22%; p = 0.003 and 89% vs. 27%; p = 0.002, respectively). PEV levels were not associated with the risk of aGVHD. Our data suggest that the measurement of cell-derived EV at engraftment can be used as a preemptive biomarker for acute GVHD.

Chronic Myelogenous Leukemia with Double Philadelphia Chromosome and Coexpression of p210 and p190 Fusion Transcripts.

The Philadelphia (Ph+) chromosome, t(9;22)(q34;q11.2), originates from a chimeric gene called BCR-ABL and is present in more than 90% of CML patients. Most patients with CML express the protein p210 BCR-ABL and, with a frequency lower than 5%, express rare isoforms, the main one being p190. In the transition from the chronic phase to the blast phase (BP), additional chromosomal abnormalities, such as the presence of the double Ph+ chromosome, are revealed. Of the 1132 patients analyzed via molecular biology in this study, two patients (0.17%) showed the co-expression of the p210 and p190 isoforms for the BCR-ABL transcript, with the concomitant presence of a double Ph+ chromosome, which was observed via conventional cytogenetics and confirmed by fluorescent in situ hybridization. The BCR-ABL/ABL% p210 and p190 ratio increased in these two patients from diagnosis to progression to blast crisis. To our knowledge, this is the first report in the literature of patients who co-expressed the two main BCR-ABL transcript isoforms and concomitantly presented Ph+ chromosome duplication. The evolution from the chronic phase to BP often occurs within 5 to 7 years, and, in this study, the evolution to BP was earlier, since disease-free survival was on average 4.5 months and overall survival was on average 9.5 months. The presence of the p190 transcript and the double Ph+ chromosome in CML may be related to the vertiginous progression of the disease.

Safety and Feasibility of Outpatient High Dose Cytarabine for Acute Myeloid Leukemia in the Brazilian Amazon.

Background: The attempt to manage patients with acute myeloid leukemia as outpatients has become increasingly common due to high hospitalization costs, low availability for beds and patient preference. Publications on the subject are scarce, especially in low-income regions and the safety in this population remains to be determined. The present study aims to assess the safety of consolidation with high-dose cytarabine in the outpatient setting. Materials and Methods: We retrospectively analyzed 39 patients who underwent consolidation with high-dose cytarabine, between 2009 and 2018, at Ophir Loyola Hospital, in Belém, Brazil. Patients treated after 2015 were given high-dose cytarabine as outpatients due to the decision of medical staff. Results: Twenty-seven patients received 76 cycles of cytarabine as outpatients; males were 48.14% of the total population, with a median age of approximately 45 years. The occurrence of delay between cycles was significantly lower among outpatients (48.14% vs. 83.33%, p = 0.04). There was no difference in relapse rates, transfusion requirements and non-relapse mortality between both groups. Hospitalization was required in 40.74% of patients during outpatient cycles and 18.51% of blood cultures were positive for pathogens. Non-relapse mortality was significantly higher among patients above 50 years old and treated on an outpatient basis (44.4% vs. 5.60%, p = 0.03). Conclusion: High-dose cytarabine administration on an outpatient basis appears to be safe and effective in a low-income population at the Brazilian Amazon region, but toxicity seems to be increased for patients older than 50 years.

Association between sarcopenia and diabetes in community dwelling elderly in the Amazon region - Viver Mais Project.

BACKGROUND: Studies indicate the intrinsic relationship between sarcopenia and diabetes mellitus (DM) pathophysiological mechanisms. Changes in insulin and muscular metabolism are features of diabetic patients and can interact as sarcopenic accelerators. Conversely, sarcopenic patients feature lower glucose tolerance and higher serum insulin levels, predisposing them to DM. OBJECTIVE: To study the association between sarcopenia and DM in a community-dwelling elderly population of the Amazon region. METHODS: Cross-sectional study, performed in Belém, Brazil, with 1078 patients aged above 60 years old from the Viver Mais Project (VMP). The definition of sarcopenia was based in the European Working Group on Sarcopenia in Older People (EWGSOP). Calf circumference >31 cm was considered normal, muscle strength was discriminated by BMI and measured with the hand grip test, and gait speed <0.8 m/s configured low performance. DM was diagnosed when reported by the patient or medical form, use of hypoglycemic medications/insulin and in the presence of fasting glucose >126 mg/dl or glycated hemoglobin (HbA1c) >6.5% on two occasions. Other medical and socio-demographic data were extracted from medical forms. RESULTS: The frequency of sarcopenia was 9.4%, while DM was present in 36.87% of the patients, and had an increased occurrence in the sarcopenic group. Female sex, advanced age, DM, coronary insufficiency, osteoporosis, body mass index, waist circumference, triglycerides and functionality were associated with sarcopenia. In multivariate analysis, sarcopenia remained strongly associated with DM (OR: 3.208, 95%CI: 1.784-5.769). CONCLUSION: This study describes strong and independent association between sarcopenia and DM. To further clarify these findings, broader prospective cohorts are necessary.

[Copaiba oil effect on urea and creatinine serum levels in rats submitted to kidney ischemia and reperfusion syndrome]. / Efeito do óleo de copaíba nos níveis séricos de ureía e creatinina em ratos submetidos à síndrome de isquemia e reperfusão renal.

PURPOSE: To evaluate the copaiba oil effect on urea and creatinine levels in rats submitted to kidney ischemia and reperfusion syndrome. METHODS: Eighteen Wistar rats (Rattus norvegicus albinus), aged between 90 and 120 days, weight between 200 g and 250 g, were allocated in 2 groups (n=9) and submitted to 50 minutes of renal ischemia and reperfusion and treated or not with copaiba oil (0.63 ml/kg daily seven days before ischemia). The nitrogen excrements were assessed at 24, 48 and 72 hours after ischemia period. RESULTS: The urea serum level was smaller (p d" 0,05) at 24 and 48 hours, and the creatinine serum level was smaller at 48 hours in animals treated with copaiba oil (GIRC) than the GIR. CONCLUSION: The copaiba oil decreased significantly the urea serum level at 24 and 48 hours and the creatinine level at 48 hours after kidney ischemia and reperfusion in rats.

Efeito do óleo de copaíba nos níveis séricos de uréia e creatinina em ratos submetidos à síndrome de isquemia e reperfusão renal / Copaiba oil effect on urea and creatinine serum levels in rats submitted to kidney ischemia and reperfusion syndrome

OBJETIVO: Avaliar o efeito do óleo de copaíba nos níveis séricos de uréia e creatinina em ratos submetidos a síndrome de isquemia e reperfusão renal. MÉTODOS: Foram utilizados 18 ratos (Rattus norvegicus albinus),da linhagem Wistar, fêmeas, adultas, entre 90 e 120 dias de idade, pesando ente 200g e 250g, distribuídos em dois grupos: Isquemia e Reperfusão (GIR), e Isquemia e Reperfusão Copaíba (GIRC). Os animais dos dois grupos foram submetidos à isquemia renal, de ambos os rins, por 50 minutos, seguida de reperfusão por 24, 48 e 72 horas, com posterior coleta de sangue e análise dos níveis séricos de uréia e creatinina. No GIRC, realizou-se, além da isquemia e reperfusão, a administração diária do óleo de copaíba na dose de 0,63 ml/kg, por gavagem, sete dias antes do procedimento de isquemia renal. RESULTADOS: Foi observada uma diminuição estatisticamente significante dos níveis séricos de uréia no GIRC em 24 e 48 horas de reperfusão renal e uma diminuição do nível sérico de creatinina no GIRC em 48 horas de reperfusão renal quando comparados com o grupo Controle. CONCLUSÃO: Segundo os procedimentos aplicados, o óleo de copaíba diminuiu os níveis séricos de uréia em 24 horas e 48 horas e os de creatinina nas 48 horas após o procedimento de isquemia e reperfusão renal em ratos.