Objectives: To assess the efficacy and toxicity of the most employed therapeutic approaches in the treatment of primary breast lymphoma (PBL). Methods: Ninety-six patients with PBL in the early stage (I or II) were enrolled to receive radiotherapy (45 Gy); chemotherapy (six cycles of cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP), every 21 days), or combined therapy. Results: Complete response was achieved in 20 of 30 patients treated with radiotherapy, 19 of 32 who were treated with chemotherapy and 30 of 34 in the combined arm (p < 0.01). Actuarial curves at 10 years showed that event-free survival was 50, 57 and 83%, respectively (p < 0.01). Actuarial curves for overall survival were 50, 50 and 76% (p < 0.01), respectively. The most common site of relapse was the central nervous system. Acute toxicity was mild. Until now, no second neoplasm or acute leukemia has been observed. Conclusions: In our study combined therapy is the best treatment in this special setting of patients; with improvement in event-free survival and overall survival without acute or severe late side effects. Prophylaxis to the central nervous system will be considered in the initial treatment to improve outcome.

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 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.

Angiocentric T cell/natural killer (NK) nasal lymphoma remains a rare clinical presentation in North America and Europe but is more common in Asia and Latin America. We have reviewed 108 cases of angiocentric T/NK cell lymphoma of the nasal cavity with a view to establishing prognostic factors. Most patients were high or high intermediate clinical risk and had additional poor prognostic factors such as bulky disease, high levels of beta 2 microglobulin, advanced stage and multiple extranodal involvement. At 8 years, overall survival was 82%, 90% and 84% for low-intermediate, high-intermediate and high clinical, respectively. Disease free survival was very similar: 79%, 83% and 80%, respectively. Multivariate analysis did not identify any factor influencing overall survival and disease-free survival. There was no evidence that the international prognostic index (IPI) was applicable in these patients and it appears that angiocentric T/NK cell lymphoma is an independent prognostic factor itself.

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.

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Residual disease in patients with diffuse large B-cell lymphoma after intensive chemotherapy remains a problem. Radiotherapy has been used in some retrospective studies without definitive conclusions. We report the first controlled clinical trial to define the role of radiotherapy in this setting of patients. One hundred and sixty-six patients with diagnosis of diffuse large B-cell lymphoma, high- or high-intermediate clinical risk, with residual disease (defined as tumor mass < 5 cm) were randomly assigned to received radiotherapy at the involved field, with 30 Gy delivered in 20 sessions or no radiation (control group). Median follow-up was 135 mo; patients who received radiotherapy have an better outcome. Actuarial curves at 10 yr showed that progressive-free disease was 86% and overall survival was 89%; those were statistical significant when compared to patients who did no received radiotherapy: 32% and 58% respectively, (p < 0.001). Toxicity was mild and well tolerated. We concluded that presence of residual mass after chemotherapy in patients with aggressive malignant lymphoma has a worse prognosis, and salvage radiotherapy improves outcome with mild toxicity. We feel that radiotherapy will be considered as necessary treatment in this special group of patients.

Treatment of patients with early stage gastric mucosa-associated lymphoid tissue (MALT) remains undefined. We began a controlled clinical trial to evaluate efficacy and toxicity of the most common therapies. Two hundred and forty-one patients with gastric low-grade MALT lymphoma in early stage (IE and IIE) were randomized to surgery (80 cases), radiotherapy (78 cases), and chemotherapy (83 cases). With a median follow-up of 7.5 yr, actuarial curves at 10 yr showed that event-free survival was 52% in patients treated with surgery, 52% in radiotherapy arm, and 87% in the chemotherapy group (p < 0.01). However, overall survival did not showed any statistical differences: 80%, 75% and 87%, respectively (p = 0.4). Acute and late toxicities were mild. No death-related treatments were observed. No clear differences were observed between the most common therapies in patients with primary gastric MALT lymphoma in early stages, probably because this type of lymphoma has an high response rate to salvage treatment after failure to local treatment (surgery and radiotherapy). Thus considered, chemotherapy alone is an effective and safe therapeutic approach in this setting of patients. Surgery or radiotherapy will be reserved to patients that are not candidates for chemotherapy.

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.