Otavio C. G. Baiocchi

Endocarditis due to glycopeptide-intermediate Staphylococcus aureus: case report and strain characterization

We report a case of infective endocarditis due to vancomycin-intermediate Staphylococcus aureus (VISA) that did not respond to high doses of vancomycin. Initial vancomycin MIC of the last isolate recovered from blood was 8 micro g/mL, but could be induced up to 32 micro g/mL by consecutive growing with vancomycin. Clinical response was only accomplished when linezolid was included in therapy.

Epstein-Barr viral load, interleukin-6 and interleukin-10 levels in post-transplant lymphoproliferative disease: a nested case-control study in a renal transplant cohort.

The possible correlation among Epstein-Barr virus (EBV) load, interleukin-6 (IL-6) and interleukin-10 (IL-10) levels has become an attractive issue and can provide a useful tool for diagnosis and monitoring of patients at risk for post-transplant lymphoproliferative disease (PTLD) development. At the time of diagnosis of PTLD, 11 patients were prospectively enrolled and 55 nested controls were selected from a 1800 renal transplant cohort. Real-time polymerase chain reaction (PCR) was used to quantify EBV load in peripheral blood mononuclear cells (PBMC). Serum IL-6 and IL-10 levels were determined using an enzyme-linked immunosorbent assay (ELISA). The median EBV load of PTLD cases was 17400 copies/10(6) PBMC, statistically different from controls (P=0.001). The median IL-6 level of PTLD cases was not different from controls (P=0.079). However, median IL-10 levels showed a significant difference in both groups (P < or = 0.001). The receiver-operating characteristic (ROC) curve analysis was applied to estimate the IL-10 cut-off value predictive of PTLD development. We found that 73.5 pg/ml has high sensitivity (1.00) and specificity (0.85). Also, Pearsons analysis showed a strong correlation between EBV load and serum IL-10 concentration (P < or = 0.001). This nested case-control study demonstrates that EBV load at diagnosis of PTLD correlates with IL-10 levels, and that monitoring of IL-10 can provide a less expensive and less time-consuming tool for PTLD diagnosis and close follow-up of patients at risk. Furthermore, we were able to define a cut-off value of IL-10 mostly predictive of PTLD development in this cohort. Our data suggest that serial measurements prior to PTLD development must be carried out to validate our hypothesis.

Primary Breast Lymphoma: An Uncommon but Curable Disease

Primary malignant breast lymphoma (PBL) is a rare disease with an incidence of 0.04-0.5% of all malignant breast neoplasms. The majority of cases are B-cell lymphomas and the most common histologic type is diffuse large B-cell lymphoma (DLCL). In this study, we report our experience with three cases of PBL. The treatment was the same currently indicated for early stage aggressive NHL, i.e. anthracycline based chemotherapy followed by the involved field radiation therapy. Unfortunately, two patients underwent mastectomy to carry out correct diagnosis. The three patients are alive without any evidence of relapse after 24, 67 and 135 months of follow-up. Considering that aggressive NHL is very sensitive to chemotherapy, mastectomy should be avoided to preserve the quality of life of these patients, once surgery does not change the good prognosis of PBL.

Megakaryocytic blast crisis as a first presentation of chronic myeloid leukemia

Abstract: Acute megakaryocytic leukemia (AmegL) corresponds to 5.0–10.0% of all acute myeloid leukemias (AML). Blast crisis as the first presentation of chronic myeloid leukemia (CML) accounts for 10.0% of all cases. Objective: We report a case of megakaryocytic blast crisis as the first presentation of CML. Case report: A 25‐yr‐old‐female with a 2‐month history of dry cough and a large, non‐tender splenomegaly was found to have a hemoglobin concentration of 10.5 g/dL, a hematocritof 33.0%, a white blood cell count (WBC) of 11.4 × 106 L with 38% small blasts, eosinophilia of 5%, basophilia of 8%, and a platelet count of 580 × 109 L. Bone marrow aspiration revealed 24% of blast cells with cytoplasmatic blebs and hyperplastic megakaryocytic lineage with dysplasia. Cytochemical stains were all negative, immunophenotyping studies showed CD41 and CD61 positivity in blast cells. Bone marrow biopsy showed grade II fibrosis. Karyotype revealed 46, XX, t(9,22) (q34.1;q11.2)[20] and the reverse‐transcriptase‐PCR (RT‐PCR) gave rise a product with a size corresponding to the 210 kDa protein (p210). No matched donor was found. After induction therapy 5.9% of blast cells persisted. The patient received Imatinib Mesylate and is doing well after a 12‐month follow‐up. Discussion: AmegL as the first presentation of CML is a rare and often fatal event. Some characteristics point towards the diagnosis of a blast crisis instead of AmegL de novo with t(9,22).

Impact of Highly Active Antiretroviral Therapy in the Treatment of HIV–Infected Patients with Systemic Non-Hodgkin‘s Lymphoma

Twenty cases of systemic non-Hodgkin‘s lymphoma (NHL) in HIV-infected patients were reviewed over a 10-year-period, divided into Group A, including 13 NHL cases treated before the highly active antiretroviral therapy (HAART) era, and Group B, including 7 patients who received HAART. A Kaplan-Meier survival curve was performed and log-rank was applied to assess statistical differences between the groups. In group A, the median CD4 count was 36 cells/mm 3 . No complete remission was found. In group B, the median CD4 count was 137 cells/mm 3 . Four patients (57.0%) are still alive and in complete remission. Group A had a median survival of 5 months and group B 31 months (p=0.0032). Our results are in agreement with recent reports in that a higher CD4 count and better immune status achieved with HAART is predictive of a better outcome. We found that HAART in combination with chemotherapy improves overall survival of NHL patients without increasing adverse effects.

Clinical correlations and prognostic relevance of HGF, VEGF AND FGF expression in Brazilian patients with non-Hodgkin lymphoma

The aims of this study were to correlate HGF, VEGF and FGF serum levels and microvessel density (MVD) with cell origin, biological behavior, tumor load and prognosis in NHL. Eighty-seven consecutive previously untreated NHL patients had serum samples collected; 37 (42%) of them also had serum follow-up samples; the control group was composed of 10 healthy blood donors. Cytokine serum levels were determined by ELISA, and MVD was measured by CD34 staining in paraffin blocks. HGF mean serum level was significantly higher in both early and advanced NHL stages when compared with the control group. HGF was also significantly higher in aggressive and indolent NHL when compared with the control group. Also, mean serum level of HGF in aggressive NHL was significantly higher than in indolent NHL. Regarding International Prognostic Index (IPI), HGF mean serum level at diagnosis was significantly higher for patients with IPI >2 when compared to IPI ≤2. Sequential analyses of HGF, VEGF and FGF serum levels in NHL showed that serum HGF and VEGF levels decreased significantly after 6 months of treatment completion. Our findings suggest that HGF serum level is associated with tumor load and aggressiveness, and response to treatment results in a decrease in HGF serum levels in NHL patients.

Impact of Epstein-Barr virus in the clinical evolution of patients with classical Hodgkin's Lymphoma in Brazil

Classical Hodgkins Lymphoma (cHL) has been frequently associated with Epstein–Barr virus (EBV), which can be found in a latent pattern in Reed‐Sternberg (RS) cells. However, the impact of the presence of EBV in RS cells and its prognosis are still controversial. We analysed the presence of EBV in RS cells and its influence in the clinical evolution of patients with cHL treated in two public hospitals in the city of São Paulo, Brazil.

Importance of combined-modality therapy for primary bone lymphoma.

Primary bone lymphoma (PBL) is a rare entity and comprises about 5% of all extranodal non-Hodgkins lymphomas (NHL) and 7% of all primary bone tumors. To date there is no consensus about the optimal treatment for PBL. We retrospectively reviewed all cases of PBL treated at Hospital São Paulo, Brazil, over a 10-year-period (January 1992-January 2002). Medical records of 7 patients with PBL were reviewed and information on age at diagnosis, sex, NHL clinical staging (CS), treatment and response to treatment were retrieved. Five patients (72%) received combined-modality therapy (CMT) and all of them are in complete remission (CR) with a median follow up of 19 months (ranging from 12 to 144 months). We conclude that PBL is a potentially curable malignancy and treatment should be undertaken in a multiprofessional approach, in order to provide the best support which probably has to include chemotherapy, radiotherapy and, for patients with IPI higher than 2, consolidation with stem-cell transplantation.Primary bone lymphoma (PBL) is a rare entity and comprises about 5% of all extranodal non-Hodgkins lymphomas (NHL) and 7% of all primary bone tumors. To date there is no consensus about the optimal treatment for PBL. We retrospectively reviewed all cases of PBL treated at Hospital São Paulo, Brazil, over a 10-year-period (January 1992-January 2002). Medical records of 7 patients with PBL were reviewed and information on age at diagnosis, sex, NHL clinical staging (CS), treatment and response to treatment were retrieved. Five patients (72%) received combined-modality therapy (CMT) and all of them are in complete remission (CR) with a median follow up of 19 months (ranging from 12 to 144 months). We conclude that PBL is a potentially curable malignancy and treatment should be undertaken in a multiprofessional approach, in order to provide the best support which probably has to include chemotherapy, radiotherapy and, for patients with IPI higher than 2, consolidation with stem-cell transplantation.

Treatment outcomes for Hodgkin lymphoma: First report from the Brazilian Prospective Registry

Data about Hodgkin lymphoma (HL) in developing countries are scarce and suggest the existence of substantial disparities in healthcare and outcomes in large areas of the world. In 2009, a prospective registry of HL was implemented in Brazil. Web‐based data were contributed by 20 institutions across the country participating in the Brazilian Prospective Hodgkins Lymphoma Registry. The aim of this study was to present the clinical features and outcomes of newly diagnosed patients with HL aged 13 to 90 years. Multivariate Cox regression models were used to estimate progression‐free (PFS) and overall survival (OS) by clinical factors. A total of 674 patients with classical HL were analysed, with a median follow‐up of 37 months. Median age was 30 years (13‐90). The median time from the onset of symptoms to diagnosis was 6 months (0‐60). Only 6% of patients had early favourable disease, while 65% had advanced disease. Stage IVB was present in 26% and a high‐risk International Prognostic Score in 38%. Doxorubicin, bleomycin, vinblastine, and dacarbazine was used in 93%. The median dose of radiotherapy was 36 Gy for localized disease and 32 Gy for advanced disease. The 3 year PFS in early favourable, early unfavourable, and advanced disease were 95%, 88%, and 66%, respectively. High‐risk International Prognostic Score, advanced disease, and age greater than or equal to 60 were independently associated with poorer PFS and OS; performance status greater than or equal to 2 was also associated with a poorer OS. Poor‐risk patients predominated. Radiation doses for localized disease appear higher than current recommendations. Outcomes appear inferior in developing countries than in developed countries. Delayed diagnosis is probably a major factor underlying these findings. Scattered reports from developing nations suggest that many aspects of standard care in developed countries remain unmet needs for populations living in developing countries. The present report contributes to this body of data, with a proper description of what is currently achieved in urban areas in Brazil.

Serum free light chains and post-transplant lymphoproliferative disorder in patients with renal transplant.

Abstract The aim of the present study was to determine whether there is an association between serum free light chains (sFLC) quantification and the development of post-transplant lymphoproliferative disorder (PTLD), using serum samples from a nested case–control cohort of patients with renal transplant. Ten new cases of PTLD and 46 controls were enrolled. Additional comparison groups consisted of five human immunodeficiency virus (HIV)-infected individuals, five with untreated Hodgkin lymphoma and six normal individuals. Serum κ and λ FLC concentrations were measured by nephelometry and compared with reference ranges (normal and renal ranges). κ and/or λ were above the normal range in 90% of cases and in 65% of matched controls. There was no statistically significant difference between all groups, except for λ FLC concentrations between cases of PTLD and normal individuals (p = 0.016). The κ/λ sFLC ratios of cases and controls were within the renal range and normal range. Our results suggest that sFLC are not useful to predict PTLD development in renal transplant recipients.