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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.

EZH2 is an important epigenetic regulator, but its role in diffuse large B‐cell lymphoma (DLBCL) pathogenesis and its relationship with MYC, BCL2, and TP53 expression, chromosomal rearrangements, and clinical features are still poorly understood. So, we investigated EZH2 expression and its associations with the immunophenotypic presentations, including MYC, BCL2, and TP53 expression, MYC, BCL2, and BCL6 translocation status, clinicopathological features, and therapeutic response to R‐CHOP in a series of 139 DLBCL cases. EZH2 positivity was associated with MYC and TP53 expression (p = 0.0002 and p = 0.0000, respectively) and to high proliferative index (Ki67>70%, p = 0.0082). No associations were found among EZH2 expression and chromosomal translocation status. The non‐germinal center (nGC) DLBCL presented most of associations observed in the general sample; however, only TP53 immunodetection showed associations with EZH2 expression in the germinal center (GC) DLBCL. EZH2 expression had no impact on therapeutic efficacy in R‐CHOP‐treated patients. In conclusion, EZH2 seems to be upregulated by MYC, to rely on TP53 alterations, and is associated with high proliferative tumors in DLBCL, which might be dependent on GC or nGC subclassifications. Furthermore, it is not a therapeutic efficacy marker to R‐CHOP in our series.

Background Natural Killer Cells are innate immune system cells important in host defenses against viruses and tumor cells. Two subpopulations are well described: NK CD56bright CD16neg (NK56++16-, lower frequency on peripheral blood-PB, high cytokine production) and NK56dim16pos (NK56+16+, higher frequency on PB, high cytotoxic activity). They are activated through a balance between signals given from activating and inhibitory receptors (KAR and KIR, respectively). The ligands of KIRs are the MHC molecules and in the absence of compatible MHC, NK cells are activated. In the allogeneic hematopoietic stem cell transplantation (HSCT), recent studies showed that NK cells recovery is important on infection control and, in the presence of a KIR-MHC mismatch, they may be important on graft versus host disease (GVHD) and graft versus leukemia effects. However few studies evaluated NK subpopulations recovery and HSCT endpoints. Objectives To evaluate the impact of NK subpopulations recovery on HSCT endpoints: relapse, GVHD, non-relapse mortality and overall survival. Patients and Methods NK (CD3-, CD56+) subpopulations (NK56++16- and NK56+16+) were quantified by multiparametric flow cytometry at 9 sequential time points (before conditioning, at engraftment, and at days 3, 7, 14, 21, 60, 100 and 180 after engraftment). Overall, 111 patients, from 4 HSCT centers (65% male, median age 17 years, range 1-74), receiving bone marrow (BM, 46%), umbilical cord (UCB, 32%) or peripheral blood (PB, 22%) from unrelated (n=90) or related donors (n=21) were studied. The most common diagnosis was acute leukemia (AML 36%, ALL 31%, MDS 9%, CML 9%, Aplastic anemia 8%). Most patients received myeloablative conditioning (MAC) regimens (60%). Antithymocyte globulin (ATG) was used in 44 patients (40%) and total body irradiation (TBI) in 56 (51%). Median follow up time was 14 months (range 4-35). Results Eighty-six patients presented sustained allogeneic recovery (no differences among sources). Of these, median time to neutrophil engraftment was 18 days (range: 8-52). The cumulative incidence (CI) of non-relapse-related mortality (NRM) was significantly higher in those with lower counts of NK56++16– during first 3 weeks after HSCT (34% at 1 year for patients with less than 30 cells/uL at day 21 vs 11% for patients with higher counts, p=0.03). Overall survival was significantly worse in patients with lower counts of NK56++16- subpopulations in the day 21 after engraftment (86% at 1 year vs 54% for patients with less than 30 cells/uL – p=0.003). CI of grade II-IV acute GVHD and relapse were not significantly affected by NK counts. The number of NK56+16+ cells did not affect any endpoint studied. Cell source, age and conditioning regimen did not affect any of the NK subpopulations counts. In multivariate analysis, NK56++16- counts lower than 30 cells/uL at 21 and 60 days after engraftment remain an independent risk factor for non relapse mortality [HR: 4.8, CI (95%): 1.2-18.8]. Conclusions Low NK56++16- counts in the first weeks after HSCT are associated with increased non relapse related mortality, but not acute GVHD or relapse. The mechanisms that rules the NK56++16- role on immunity deserve further investigations. Disclosures: No relevant conflicts of interest to declare.

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 highdose 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. Nonrelapse 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.

Case-control study based on the immunohistochemistry for TGF-β1 evaluation of cervical samples obtained from two groups of women: CIN/HIV- and CIN/HIV+. Eleven women infected with HIV and with a histopathological diagnosis of CIN were included. The control group consisted of 12 patients with CIN. Cervical tissue samples obtained from all patients were submitted to histopathology and semiquantitative analysis of immunostaining for TGF-β1 protein. In addition, the peripheral CD4+ cell count and viral load were evaluated in HIV + patients. Tissue expression of the cytokine was higher in the CIN/HIV+ group compared to control (p = 0.0023). In addition, higher TGF-β1 expression was observed in higher grade cervical lesions in the two groups. There was a trend toward a direct correlation between peripheral CD4+ T cell count and tissue TGF-β1, and toward an inverse correlation between viral load and cytokine expression. Thus, TGF-β1 was more marked in situations in which cervical lesions are known to present a more aggressive behavior, suggesting that this cytokine is involved in the pathogenesis of tumor growth in these lesions. Tissue expression of TGF-β1 is increased in cervical samples from HIV-infected women with CIN.

INTRODUÇÃO: Micose fungoide (MF) é um tipo de linfoma cutâneo de células T com incidência aproximada de 0,41/100.000 indivíduos anualmente. O presente relato ressalta os impactos do atraso diagnóstico na evolução da doença. RELATO DO CASO: Paciente do sexo feminino buscou assistência médica no serviço de dermatologia da Universidade do Estado do Pará (UEPA), em novembro de 2017, apresentando três placas eritemato-hipercrômicas infiltradas, duas no abdômen e uma descamativa no membro inferior esquerdo, e linfonodo palpável na região inguinal esquerda com crescimento progressivo que iniciou em 2011. A paciente relatou que havia sido submetida a vários exames e tratamentos, assistida por seis profissionais médicos de diferentes especialidades e realizado quatro exames histopatológicos. O caso foi investigado no serviço de dermatologia, tendo sido realizado estudo imunohistoquímico e concluído o diagnóstico de MF. A paciente iniciou tratamento com metotrexato 15 mg e ácido fólico 5 mg, em dose única semanal, e fototerapia com PUVA, tendo apresentado melhora significativa, porém, com extensa área de atrofia e infecções secundárias. CONCLUSÃO: O presente caso é um problema de saúde pública que reforça a necessidade de capacitação adequada de médicos para identificação e tratamento precoce de MF.

Introduction Given the variety of highly effective therapies available for chronic lymphocytic leukemia (CLL), a tailored treatment strategy is needed. Fixed-duration chemoimmunotherapy can produce sustained and deep responses. The presence of minimal residual disease (MRD) has been studied as an independent prognostic factor for long-term survival in patients with CLL. Multiple novel agents have been recently approved for previously untreated patients, including the BTK inhibitor, ibrutinib, but its effect on MRD is still unclear. We performed a prospective clinical trial to evaluate the efficacy of maintenance therapy with ibrutinib in patients with detectable MRD after first-line chemoimmunotherapy. Patients and methods In this phase 2 clinical trial, we assessed the efficacy and safety of ibrutinib 420 mg daily as maintenance therapy, until progression or unacceptable toxicity, after achieving complete remission (CR) or partial remission (PR) with chemoimmunotherapy in previously untreated 40 patients with CLL from 9 centers in Brazil. The median age was 60 years (range: 43-85 years). Twenty-nine patients (73%) had been treated with fludarabine and cyclophosphamide (FC) ± rituximab, 10 (25%) with chlorambucil ± rituximab, and one (2%) with bendamustine + rituximab. Responses definitions were based on the 2018 iwCLL guidelines. Twenty-five patients (63%) were in CR and 15 (37%) in PR before the start of maintenance. Patients with detectable MRD within 12 months after the end of the first line chemoimmunotherapy were included. Besides, three patients with undetectable MRD were also included in order to evaluate possible effects of ibrutinib on that group. Responses were assessed monthly during the first year and every three months thereafter. MRD was assessed by 8-color flow cytometry in the bone marrow and in the peripheral blood before and after one year of maintenance therapy, and in peripheral blood every 3 months thereafter. Primary end point was progression-free survival (PFS). Results Median follow-up time was 25 months (range: 12-46 months). Among the 40 patients included, two patients withdrew consent (one just after inclusion and one after 30 days), and one patient died 7 days after ibrutinib was started due to an unrelated cause (ruptured aortic aneurysm). Thirty-seven patients were treated with ibrutinib and prospectively followed. The median PFS and overall survival (OS) were not reached. PFS and OS at 2 years were 92% and 95%, respectively. Among the 15 patients who started maintenance in PR, 8 (53%) achieved CR (3 of which had incomplete hematologic recovery), and 7 had complete nodal response, but remained in PR due to persistent lymphocytosis. Among the 22 who entered maintenance in CR, all but one remained in CR: 1 patient presented ≥ 50% increase in his baseline lymphocyte count 40 months after maintenance was started, but remains on ibrutinib with no cytopenias or clinical indication to treatment change. Among the 34 patients who had detectable MRD, 9% had at least 1-log reduction after one year and 20% after 2 years. Besides, one patient achieved undetectable MRD so far, 30 months after ibrutinib was started. All 3 patients with undetectable MRD at baseline, remained undetectable. Sustained increases from baseline values in the hemoglobin and platelet levels were observed in 30 patients (81%). Adverse events of any grade that occurred during maintenance with ibrutinib included diarrhea (23%), nausea (10%), and fatigue (8%), but only 2 patients had grade 3 diarrhea, associated with the concomitant use of metformin that resolved after discontinuation. Atrial fibrillation occurred intermittently in 3 patients during maintenance. A total of 81% of patients remain on ibrutinib. Four patients discontinued the drug: one after 8 months to perform a stem cell transplant by the decision of the treating physician, one after 10 months due to adverse events (lymphomatoid granulomatosis), and 2 after 13 months due to logistic difficulties to remain on regular follow up. Conclusions Maintenance with ibrutinib for CLL patients achieving CR or PR after chemoimmunotherapy resulted in excellent PFS and OS, and sustained improvement in hematologic variables irrespectively of achieving undetectable MRD. Efficacy of this regimen compares well to other frontline chemo-free treatments offered to patients with CLL in the United States and Europe. Disclosures No relevant conflicts of interest to declare.