Low-dose radiotherapy (2×2 g) versus low doses and rituximab in the treatment of marginal zone b-cell lymphoma previously untreated.

Radiotherapy (RT)is considered the treatment of choice in patients with Extra-nodal marginal zone lymphoma (EMZL) at early stage, but the presence of late toxicities has been limited the acceptance. Recently, low doses of RT LDR) (2 x 2 Gy) and the use of limited fields has been observed that retain the efficacy but eliminate toxicities; rituximab is considered as a single agent useful in these setting of patients. Thus, we conducted a open label study to evaluate the use of LDR compared with LDR and rituximab, in a large number of patients without previous treatment. METHODS: Patients with pathological diagnosis or(EMZL)), stage I, without previous treatment, were allocated in a proportion 1:1 to received LDR) that were compared with a group that received LDR and rituximab. RESULTS: One hundred and fourteen patients were recruit ; overall response rate and complete response were : 58(98.3%) and 54 (96.4 %)in patients whose respectively in LDR that were no statistical different to the observed in the LDR + R arm: 53 (96.3%) and 51 (92.75 %) respectively. Actuarial curves at 5-years show that progression-free survival in LDR arm were: 98.4% (95% Confidence interval (CI): 93%-108%) and OS were 97.2% (95%CI: 92%-110%), that did no show statistical difference with the LDR-R arm: 96.4% (95%CI: 90%-110%), and 98.5%(95%CI:92%-107%) respectively. Univariate analysis did not show any statistical differences in the analysis of prognostic factors. Acute and late toxicities were not observed. CONCLUSION: We conclude that LDR will be considered as the treatment of choice in patients with EMZL, in early stage, localized in head and neck anatomical sites; because response and outcome were excellent, without any toxicity, addition of rituximab did not improve results and outcome.

Retracted article: Adjuvant radiotherapy in patients with diffuse large B-cell lymphoma in advanced stage (III/IV) improves the outcome in the rituximab era.

Statement of Retraction: Adjuvant radiotherapy in patients with diffuse large B-cell lymphoma in advanced stage (III/IV) improves the outcome in the rituximab era We, the Editor[s] and Publisher of Hematology, have retracted the following article: Avilès, A, Nambo, M-J, Calva, A, et al. Adjuvant radiotherapy in patients with diffuse large B-cell lymphoma in advanced stage (III/IV) improves the outcome in the rituximab era. Hematology. 2019;24:507-511; DOI: 10.1080/10245332.2018.1423880 The above article has been retracted as a result of concerns regarding the data upon which the presented research has been based. After re-examination and several independent expert reviews the consensus is that the data and results are not reliable and therefore the article must be retracted. The authors have agreed with this decision. We have been informed in our decision-making by our policy on publishing ethics and integrity and the COPE guidelines on retractions. The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as "Retracted".

Prolonged Use of Zoledronic Acid (4 Years) Did Not Improve Outcome in Multiple Myeloma Patients.

BACKGROUND: Bisphosphonates, especially zoledronic acid (ZA), show antitumor effects in multiple myeloma (MM) and other neoplasms. The standard time for ZA administration has been 2 years. However, with improvement in overall survival (OS) in MM with new agents, it unclear whether ZA could be administered for a prolonged time to improve OS. PATIENTS AND METHODS: A total of 170 patients with untreated, symptomatic MM were randomly divided into a group to receive ZA for 4 years, with a control group to receive ZA for 2 years. All patients were treated with the same induction therapy and stem-cell transplantation. RESULTS: Actuarial curves at 5 years, showed that progression-free survival was 75% (95% confidence interval [CI], 64%-82%) and OS was 68% (95% CI, 60%-76%) in the 4-year group, which was not statistically significantly different compared with the control group: 72% (95% CI, 62%-78%) and 68% (95% CI, 60%-75%; P = .67). However, the 4-year group showed reduced skeletal events (21% occurrence rate); this was statistically significant compared with the control group: 43% (P < .001). CONCLUSION: Although ZA did not improve OS in patients with MM; it continued to be useful to reduce skeletal events, and thus improve better quality of life for patients.

Hemodiafiltration Decreases Serum Levels of Inflammatory Mediators in Severe Leptospirosis: A Prospective Study.

BACKGROUND: Leptospirosis is a health problem worldwide. Its most severe form is a classic model of sepsis, provoking acute respiratory distress syndrome (ARDS) and acute kidney injury (AKI), with associated mortality that remains unacceptably high. We previously demonstrated that early initiation of sustained low-efficiency dialysis (SLED) followed by daily SLED significantly decreases mortality. However, the mode of clearance can also affect dialysis patient outcomes. Therefore, the objective of this study was to compare the effects of SLED with traditional (diffusive) clearance, via hemodialysis, and SLED with convective clearance, via hemodiafiltration (SLEDf), in patients with severe leptospirosis. METHODS: In this prospective study, conducted in the intensive care unit (ICU) from 2009 through 2012, we compared two groups-SLED (n = 19) and SLEDf (n = 20)-evaluating demographic, clinical, and biochemical parameters, as well as serum levels of interleukins, up to the third day after admission. All patients received dialysis early and daily thereafter. RESULTS: During the study period, 138 patients were admitted to our ICU with a diagnosis of leptospirosis; 39 (36 males/3 females) met the criteria for ARDS and AKI. All patients were on mechanical ventilation and were comparable in terms of respiratory parameters. Mortality did not differ between the SLEDf and SLED groups. However, post-admission decreases in the serum levels of interleukin (IL)-17, IL-7, and monocyte chemoattractant protein-1 were significantly greater in the SLEDf group. Direct bilirubin and the arterial oxygen tension/fraction of inspired oxygen ratio were significantly higher in the SLED group. We identified the following risk factors (sensitivities/specificities) for mortality in severe leptospirosis: age ≥ 55 years (67%/91%); serum urea ≥ 204 mg/dl (100%/70%); creatinine ≥ 5.2 mg/dl (100%/58%); Acute Physiology and Chronic Health Evaluation II score ≥ 39.5 (67%/88%); Sequential Organ Failure Assessment score ≥ 20.5 (67%/85%); and inspiratory pressure ≥ 31 mmHg (84%/85%). CONCLUSIONS: The mode of dialysis clearance might not affect outcomes in severe leptospirosis.

Hemodiafiltration decreases serum levels of inflammatory mediators in severe leptospirosis: A prospective study

BACKGROUND: Leptospirosis is a health problem worldwide. Its most severe form is a classic model of sepsis, provoking acute respiratory distress syndrome (ARDS) and acute kidney injury (AKI), with associated mortality that remains unacceptably high. We previously demonstrated that early initiation of sustained low-efficiency dialysis (SLED) followed by daily SLED significantly decreases mortality. However, the mode of clearance can also affect dialysis patient outcomes. Therefore, the objective of this study was to compare the effects of SLED with traditional (diffusive) clearance, via hemodialysis, and SLED with convective clearance, via hemodiafiltration (SLEDf), in patients with severe leptospirosis. METHODS: In this prospective study, conducted in the intensive care unit (ICU) from 2009 through 2012, we compared two groups-SLED (n = 19) and SLEDf (n = 20)-evaluating demographic, clinical, and biochemical parameters, as well as serum levels of interleukins, up to the third day after admission. All patients received dialysis early and daily thereafter. RESULTS: During the study period, 138 patients were admitted to our ICU with a diagnosis of leptospirosis; 39 (36 males/3 females) met the criteria for ARDS and AKI. All patients were on mechanical ventilation and were comparable in terms of respiratory parameters. Mortality did not differ between the SLEDf and SLED groups. However, post-admission decreases in the serum levels of interleukin (IL)-17, IL-7, and monocyte chemoattractant protein-1 were significantly greater in the SLEDf group. Direct bilirubin and the arterial oxygen tension/fraction of inspired oxygen ratio were significantly higher in the SLED group. We identified the following risk factors (sensitivities/specificities) for mortality in severe leptospirosis: age ≥ 55 years (67%/91%); serum urea ≥ 204 mg/dl (100%/70%); creatinine ≥ 5.2 mg/dl (100%/58%); Acute Physiology and Chronic Health Evaluation II score ≥ 39.5 (67%/88%); Sequential Organ Failure Assessment score ≥ 20.5 (67%/85%); and inspiratory pressure ≥ 31 mmHg (84%/85%). CONCLUSIONS: The mode of dialysis clearance might not affect outcomes in severe leptospirosis

Speckle-Tracking Echocardiography to Detect Cardiac Toxicity in Children Who Received Anthracyclines During Pregnancy.

Cardiac toxicities remain a possible risk to fetuses that received anthracyclines during pregnancy. The introduction of new echocardiographic techniques will improve the detection of early cardiac damage. Thus, we began a observational study using speckle-tracking echocardiography (STE) in children who had received anthracyclines during pregnancy, including the first trimester. From 2009 to 2013, we performed STE on patients > 5 years old, whose mothers had received anthracyclines during pregnancy. Siblings or cousins of equivalent age and gender were used as the control group. A total of 90 children fulfilled the entry criteria. Our results with STE were normal in all echocardiography parameters and did not show any differences when compared with the findings from the control group. We consider that the use of anthracyclines during pregnancy does not produce cardiac damage in newborns and can be safely administered, because no cardiac toxicity was evident in these children and it is of benefit to the mother.

Ensaio clínico aleatorizado avaliando o impacto de diferentes métodos de terapia renal substitutiva (TRS) na leptospirose grave

A leptospirose é um problema de saúde em todo o mundo. Sua forma mais grave, a Síndrome de Weil, é um modelo clássico de sepse, que pode provocar síndrome da angústia respiratória aguda e injúria renal aguda, este quadro clinico esta associado a mortalidade que continua a ser inaceitavelmente alta. Nós descrevemos em um estudo anterior os efeitos da dose de hemodiálise na doença de Weil, usando diálise baixa eficiência (SLED), e demonstraram que o início precoce da SLED com realizações de diálises diárias diminui significativamente a mortalidade. No entanto, a melhora do clearance pode também afetar os resultados dos doentes em diálise. Hemofiltração e hemodiálise podem proporcionar convecção ou difusão respectivamente. A hemofiltração supostamente proporciona uma maior depuração de moléculas maiores, portanto, pode beneficiar pacientes com IRA, filtrando uma quantidade maior de citocinas inflamatórias. METODOLOGIA: Ensaio clínico prospectivo, aleatorizado, realizado na UTI do IIER, especializado no tratamento de doenças infectocontagiosas, no período de janeiro de 2009 a dezembro de 2012. Comparamos dois grupos: hemodiálise estendida (SLED) x hemodiafiltração estendida (SLEDf). Avaliamos variáveis clínicas e demográficas, dados de função renal, dados bioquímicos da admissão e gravidade. Analisamos também dosagens séricas de interleucinas (ILs) nos três primeiros dias de internação, sendo a primeira amostra imediatamente ao início do tratamento dialítico. Os dois grupos receberam diálise diária e precoce. Para a determinação da diferença entre os grupos, um valor p ≥ 0,05 foi considerado estatisticamente significativo. As variáveis impactantes na estimação do óbito foram feitas segundo análises univariadas de médias, e para determinar o melhor ponto de cortes (PC) destas variáveis quantitativas na estimação do óbito com certa sensibilidade e especificidade, usamos a análise de Curva ROC...

Leptospirosis is a health problem worldwide. Its most severe form, Weil’s disease, is a classic model of sepsis, provoking acute respiratory distress syndrome and acute kidney injury (AKI), with associated mortality that remains unacceptably high. We previously described the effects of hemodialysis dose in Weil’s disease, using sustained low-efficiency dialysis (SLED), and demonstrated that early initiation of SLED followed by daily SLED significantly decreases mortality. However, the mode of clearance can also affect dialysis patient outcomes. Hemofiltration and hemodialysis can provide convective or diffusive clearance, respectively; hemofiltration reportedly provides greater clearance of medium-size and large molecules and thus might benefit critically ill AKI patients by clearing more large-molecule toxic inflammatory cytokines. Therefore, we compared the effects of convective clearance, using hemofiltration (SLEDf), and diffusive clearance, using hemodialysis (SLED), in Weil’s disease patients.In a prospective, randomized clinical trial, conducted in the ICU from 2009 through 2012, we compared two groups—SLED (n= 19) and SLEDf (n= 20)—evaluating demographic, clinical and biochemical parameters, as well as serum levels of interleukins, up to the 3rd day after admission. Both groups received early, daily dialysis.All patients received norepinephrine and were on mechanical ventilation. Although clinical data, demographic profiles and severity (SOFA/APACHE scores) were similar, TNF-α, IL-2 and IL-5 were higher in SLEDf patients than in SLED patients. Over a 3-day period, IL-7, IL-17 and MCP-1 trended lower in SLEDf patients than in SLED patients. Duration of mechanical ventilation, length of ICU stay and mortality did not differ between the groups. In a logistic mortality model, the area under the ROC curve...

Early identification of leptospirosis-associated pulmonary hemorrhage syndrome by use of a validated prediction model.

OBJECTIVE: To identify prediction factors for the development of leptospirosis-associated pulmonary hemorrhage syndrome (LPHS). METHODS: We conducted a prospective cohort study. The study comprised of 203 patients, aged > or =14 years, admitted with complications of the severe form of leptospirosis at the Emílio Ribas Institute of Infectology (Sao Paulo, Brazil) between 1998 and 2004. Laboratory and demographic data were obtained and the severity of illness score and involvement of the lungs and others organs were determined. Logistic regression was performed to identify independent predictors of LPHS. A prospective validation cohort of 97 subjects with severe form of leptospirosis admitted at the same hospital between 2004 and 2006 was used to independently evaluate the predictive value of the model. RESULTS: The overall mortality rate was 7.9%. Multivariate logistic regression revealed that five factors were independently associated with the development of LPHS: serum potassium (mmol/L) (OR = 2.6; 95% CI = 1.1-5.9); serum creatinine (micromol/L) (OR = 1.2; 95% CI = 1.1-1.4); respiratory rate (breaths/min) (OR = 1.1; 95% CI = 1.1-1.2); presenting shock (OR = 69.9; 95% CI = 20.1-236.4), and Glasgow Coma Scale Score (GCS) < 15 (OR = 7.7; 95% CI = 1.3-23.0). We used these findings to calculate the risk of LPHS by the use of a spreadsheet. In the validation cohort, the equation classified correctly 92% of patients (Kappa statistic = 0.80). CONCLUSIONS: We developed and validated a multivariate model for predicting LPHS. This tool should prove useful in identifying LPHS patients, allowing earlier management and thereby reducing mortality.

Rituximab and dose-dense chemotherapy in primary testicular lymphoma.

BACKGROUND: Treatment of primary testicular lymphoma (PTL) remains unsatisfactory even in patients with good prognosis, as < 30% of patients are alive at 3 years. PATIENTS AND METHODS: We began a phase II study to assess efficacy and toxicity of a dose-dense cyclophosphamide/epirubicin/vincristine/prednisone (CEOP14) regimen with rituximab (CEOP14R) in 38 previously untreated patients with PTL with early-stage (I or II) and low-risk disease, followed by adjuvant radiation therapy and central nervous system prophylaxis. RESULTS: Complete response was 86% (similar to historical controls), but improvement in outcome was observed; with actuarial curves at 5 years, event-free survival was 70%, and overall survival was 66%. Toxicity was mild, and the regimen was well tolerated. CONCLUSION: The addition of rituximab to dose-dense chemotherapy improves outcome in this setting of patients who previously had been considered to have the poorest prognosis. It is important that these findings will be validated in multicentric, controlled clinical trials.

Rituximab and chemotherapy in primary gastric lymphoma.

PURPOSE: We performed a phase II clinical trial to assess the efficacy and toxicity of the addition of rituximab and conventional chemotherapy in primary gastric lymphoma (PGL). METHODS: Forty-two (42) patients with PGL, stage IE and IIE, and with low- or low-intermediate clinical risk were treated in a prospective longitudinal study with standard CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) chemotherapy and rituximab (375 mg/m2, intravenously) on day 1 of each cycle administered every 21 days, for 6 cycles. The endpoint was to assess improvement in outcome measured by prolongation in event-free survival (EFS) and overall survival (OS). Complete response was achieved in 40 cases (95%) (95% confidence interval [CI]: 88%-102%). Relapse was observed in 2 cases. Two (2) patients died secondary to tumor progression. Thus, actuarial 5-year EFS was 95% (95 % CI: 87%-104%) and OS was 95% (95% CI: 88%-101%), which was not statistically different to historic controls. Acute toxicity was minimal and well tolerated, 4 cases developed late toxicity, 2 cases of herpes zoster infection, and 2 cases with granulocytopenia; in 1 case, the patient continued with mild granulocytopenia 3 years after treatment. CONCLUSIONS: The addition of rituximab to CHOP chemotherapy did not improve outcome in early-stage PGL.

Results of a phase III clinical trial: CHOP versus CMED in peripheral T-cell lymphoma unspecified.

We performed a controlled clinical trial to define the use of a brief therapy: CMED (cyclophosphamide, etoposide, methotrexate, and dexamethasone) compared with standard CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) in the treatment of peripheral T-cell lymphoma unspecific (PTCLu). The end point to the study was to assess efficacy, measured from complete response rate (CRR), progression-free survival (PFS), and overall survival in 217 previously untreated patients with PTCLu. In an intent-to treat analysis all patients were evaluable. CRR was 76% in CMED regimen and 57% in CHOP arm (P<0.05); actuarial curves at 10 years showed that PFS was 70% and 43%, respectively (P<0.01); overall survival was 60% and 34%, respectively (P<0.01). Adjuvant radiotherapy was employed in 48 cases (54% of patients who achieve CR in CMED arm) and 30 patients (47% of patients who achieve CR in CHOP arm). Acute toxicity was mild and well tolerated. Our results showed that the CMED regimen is feasible and effective in PTCLu.

Interferon and low dose methotrexate improve outcome in refractory mycosis fungoides/Sézary syndrome.

Treatment of refractory mycosis fungoides and Sézary syndrome remain unsatisfactory. In this study, we assessed the efficacy and toxicity of low-dose methotrexate (10 mg/m(2), biweekly) and interferon (9.0 MU, three times a week) as induction therapy by 6 or 12 months, followed, if patients achieved a complete remission, by interferon maintenance until toxicity or relapse. In an intent-to-treat analysis, 158 patients were considered evaluable. Complete response (biopsy proven) was observed in 112 patients (49 [31%] at 6 months and 63 [49%] at 12 months); thus, the complete response rate was 74%. With a median follow-up of 155 months (range, 62-181), progression-free disease was 71% and overall survival was 69%. Acute toxicity was mild, treatment was well tolerated, and to date no late toxicity has been observed. We conclude that this regimen is a benefit to this setting of patients, with excellent outcome and mild toxicity.

Antitumor effect of zoledronic acid in previously untreated patients with multiple myeloma.

Bisphophonates are the treatment of choice to prevent skeletal events in patients with multiple myeloma. Some preclinical studies suggested that bisphophonates can be useful as antitumor drugs in some malignancies. We conducted a controlled clinical trial to assess if zoledronic acid can have this clinical activity. Ninety four patients with previously untreated multiple myeloma were treated with a conventional chemotherapy program: cyclophosphamide, vincristine, melphalan, and prednisone (CVMP) and were randomized to received either zoledronic acid (4 mg, iv, every 28 d) or not (control group). The end-point of the present study was to assess improvement in outcome, measured by event-free survival (EFS) and overall survival (OS), and the second-end point was to confirm the efficacy in preventing skeletal events. In an intent-to-treat analysis, all patients were available for efficacy and toxicity. Median follow up was 49.6 mo (range: 34-72 mo). Five year actuarial curves showed that EFS was 80% in the zoledronic acid group, which was statistically different from 52% in the control group (p < 0.01). Actuarial 5 yr OS was 80% in the zoledronic acid arm, and 46% in the control group (p < 0.01). Sketeletal events were more frequent in the control group when compared to zoledronic acid. Toxicity was mild. We confirm the efficacy of zoledronic acid to prevent skeletal events, but we felt that we can demonstrate that zoledronic acid has a clinical antitumor effect measured from a increase in complete response rate and EFS and OS that were better when compared with the control group. We began a controlled clinical trial with modern treatment (including transplant procedures) in combination with zoledronic acid to define the role of zoledonic acid in this setting of patients.

Door-to-dialysis time and daily hemodialysis in patients with leptospirosis: impact on mortality.

BACKGROUND: Leptospirosis is a public health problem, the severe form of which (Weil's disease) includes acute respiratory distress syndrome, typically accompanied by acute kidney injury (AKI), and is associated with high mortality rates. Recent evidence suggests that dialysis dosage affects outcomes in critically ill patients with sepsis-induced AKI. However, this population varies widely in terms of age, gender, and concomitant conditions, making it difficult to determine the appropriate timing (door-to-dialysis time) and dialysis dosage. DESIGN, SETTING, PARTICIPANTS, AND MEASUREMENTS: It is logical to assume that increasing the dialysis dosage would minimize uremic complications and improve outcomes in such patients. Patients with Weil's disease constitute a homogeneous population and are typically free of comorbidities, therefore presenting an ideal model in which to test this assumption. RESULTS: The effects of dialysis dosage were evaluated in this population, with the use of either classic or slow low-efficiency hemodialysis, and two periods/treatment plans were compared: 2002 to 2003/delayed, alternate-day dialysis (DAdD group; n = 15) and 2004 to 2005/prompt and daily dialysis (PaDD group; n = 18). Age, gender, AKI severity, APACHE score, serum urea, and time to recovery of renal function were assessed. All patients received vasoactive drugs (because of hemodynamic instability) and were on mechanical ventilation (because of acute respiratory distress syndrome). Mean serum urea during the dialysis period was significantly lower in the PaDD group than in the DAdD group. Of the PaDD group patients, three (16.7%) died, compared with 10 (66.7%) of the DAdD group patients. CONCLUSIONS: On the basis of this result, it is believed that alternate-day hemodialysis is no longer appropriate for critically ill patients with Weil's disease.

Dose dense (CEOP-14) vs dose dense and rituximab (CEOP-14 +R) in high-risk diffuse large cell lymphoma.

To assess efficacy and toxicity of rituximab and dose chemotherapy in high-risk diffuse large cell lymphoma, we conducted a controlled clinical trial to assess efficacy and toxicity of a dose-dense regimen CEOP- 14 (cyclophosphamide, epirubicin, vincristine, and prednisone every 14 d) compared to CEOP-14 plus rituximab. One hundred and ninety-six patients were randomized to received CEOP-rituximab (cyclophosphamide 1500 mg/m2, epirubicin 120 mg/m2, vincristine, and prednisone at standard dose and rituximab at 375 mg/m2) compared with the same chemotherapy administered every 14 d (CEOP-14). In an intent-to-treat analysis all patients were available for efficacy and toxicity. Complete response in CEOP-14 was observed in 73 cases (74%) and in 75 patients (76%) in the CEOP-R regimen (76%) (p = 0.8). With a median follow-up of 53.4 mo, median has not been reached in time to tumor-progression (TTP) and overall survival (OS). Actuarial curves at 5 yr showed that TTP and OS in patients treated with CEOP-R were 74% and 67%, respectively, that were not statistical different when compared to CEOP-14, 72% and 65%, respectively (p = 0.8). Acute toxicity was mild and well tolerated. The use of a dense-dose regimen is useful and well tolerated in patients with very high risk diffuse large cell lymphoma. The addition of rituximab did not improve outcome in these setting of patients.

Rituximab and dose dense chemotherapy in primary breast lymphoma.

Treatment of primary breast lymphoma (PBL) remains unsatisfactory. We assess a clinical study to evaluate efficacy and toxicity of a dose dense regimen (CEOP-14) and rituximab in 32 previously untreated female patients with PBL in early stage. There was no difference in complete response rate (87%), event free-survival (75%) and overall survival (63%) compared with historical patients.

Rituximab and escalated chemotherapy in elderly patients with aggressive diffuse large-cell lymphoma: a controlled clinical trial.

The treatment of elderly patients with aggressive malignant lymphoma has not been defined. The addition of rituximab to conventional chemotherapy has been reported to improve the outcome, but most patients have good prognostic factors (performance status < 2, no severe associated diseases, low or low-intermediate clinical risk). Thus, we developed a combined regimen, including escalated doses of anthracycline and rituximab. The endpoint was to improve event-free survival (EFS) and overall survival. Two hundred and four (204) patients were randomly assigned to receive an escalated chemotherapy regimen (CEOP) with escalated dose of epirubicin, compared to the same regimen and addition of rituximab. All patients had poor prognostic factors: high- or high-intermediate clinical risk, poor performance status, bulky disease, and more than 2 with extranodal involvement. In an intent-to-treat analysis, all patients were evaluable for efficacy and toxicity. The complete response rates were similar in both arms: 74% in chemotherapy and 78% in the rituximab + chemotherapy program. EFS and overall survival were similar: 77% and 84%, respectively, in combined chemotherapy and 75% and 81% in the rituximab-chemotherapy regimen. Toxicity was mild and well tolerated. In elderly patients with diffuse large-cell lymphoma and poor prognostic factors, rituximab did not improve their outcome.

CMED in the treatment of nasal natural killer cell lymphoma with distant metastases.

INTRODUCTION: Nasal natural killer (NK) cell lymphoma that showed distant metastases generally showed an poor prognosis. We described a group of patients with these atypical presentation and that were treated with an intensive, short chemotherapy/radiotherapy regimen. METHODS: Sixty-one patients fulfilled the criteria for NK cell lymphoma with distant metastases and all have very poor prognostic factors: high clinical risk, multiple extranodal presentation and bulky disease (tumor mass >10 cm). They were treated with CMED (cyclophosphamide 2000 mg/m(2), iv, day 1, methotrexate 400 mg/m(2), iv, day 1(with leucovorin rescue), etoposide 400 mg/m(2) twice and dexametasone 40 mg daily for 4 days). If complete response (CR) was observed, they were received adjuvant radiotherapy (50 Gy) to nasal region. Patients with failure were treated with different salvage treatments. RESULTS: Forty nine patients achieved CR and 12 were considered failure, all patients that were failure and nine that relapse die secondary to tumor progression. Median follow-up were 46 months (range 34-68 months). Median has not been observed in relapse-free survival (RFS) and overall survival (OS). Actuarial curves at 5 years showed that RFS was 81% and OS was 65%. Treatment was well tolerated. CONCLUSIONS: Nasal NK cell lymphoma with distant metastases is considered an rare clinical entity, probably is under diagnosis because it has been included as stage III and IV in previous reports, that showed an very poor RFS and OS. The treatment herein report could achieve good response and outcome, but it is evident that more specific and aggressive therapy is necessary in these setting of patients.

Avaliação do impacto da diálise precoce e diária em pacientes com leptospirose grave com insuficiência renal aguda e necessidade de ventilação mecânica invasiva / Door-to-dialysis time and daily hemodialysis in patients with leptospirosis-related acute respiratory distress syndrome and acute kidney injury: impact on mortality

A forma mais grave da Leptospirose, conhecida também como Síndrome de Weil, pode ser caracterizada por injúria pulmonar grave ou insuficiência renal aguda (IRA); e quando estão associadas há um aumento da mortalidade. Estudos têm demonstrado que a dose da diálise pode afetar o prognóstico e a evolução dos pacientes em sepse. Entretanto o estudo desta população em sepse é muito difícil, pois existe uma variabilidade muito grande das características destes pacientes e das doenças aossociadas como, por exemplo, pacientes com distúrbios hematológicos, bronquíticos, portadores de insuficiência cardíaca, portadores de AIDS, hepatopatas, etc. É sabido que o aumento da dose de diálise melhora as condições metabólicas e os distúrbios hidroeletrolíticos. Os pacientes com leptospirose constituem uma população homogênea geralmente sem comorbidades associadas, portanto se apresentando então como um modelo ideal para testar esta hipótese. Nós avaliamos os efeitos da dose de hemodiálise nesta população utilizando a hemodiálise clássica ou de baixa eficiência (SLED) comparando dois grupos tratados durante períodos diferentes. Comparamos a frequência e o tempo de início da diálise nestes dois grupos. Grupo I: diálise em dias alternados e Grupo II: diálise precoce e diária...