Pilot clinical study of carmustine associated with a lipid nanoemulsion in combination with vincristine and prednisone for the treatment of canine lymphoma.

A lipid nanoemulsion (LDE) resembling low-density lipoprotein can target malignant tumours. In in vivo and clinical studies, association of chemotherapeutic agents to LDE decreased their toxicity and increased pharmacological action. Here, safety of LDE as carmustine carrier (50 mg m(-2) , intravenous) combined with vincristine and prednisone for the treatment of dogs with lymphoma was tested and compared with commercial carmustine with vincristine and prednisone. In five dogs from LDE-carmustine and six from commercial carmustine, complete remission was achieved (P > 0.05). Partial remission occurred in two dogs from each group. In both groups, the median progression-free intervals (119 and 199 days) and overall survival times (207 and 247 days) were equal. Neutropenia was observed in both groups, but no other major toxicities occurred. Therefore, no difference was observed between the treatments. LDE-carmustine was shown to be safe and effective in a drug combination protocol, which encourages larger studies to investigate the use of this novel formulation to treat canine lymphomas.

Circumscribed lesion of the medial forebrain bundle area causes structural impairment of lymphoid organs and severe depression of immune function in rats.

Interactions between the immune system and the brain are a key element in the pathophysiology of diseases such as multiple sclerosis, neuroAIDS, and Alzheimer's, which affect large numbers of individuals and are associated with a high social cost. However, the neuroanatomical basis of brain-immune interactions has not been elucidated. We report that in Wistar rats of either sex bilateral electrolytic lesion of the medial forebrain bundle reduces body weight by 28% 7 days after lesioning, and causes widespread infections, aphagia, adypsia, structural damage to the lymphoid organs and heavy depression of T lymphocytes cytotoxicity. The following alterations occur in the immune system after those lesions: the weight of the thymus, spleen and lymphonodes is reduced by 77.9%, 49.1% and 48.4%, respectively. The thymus is atrophied and contains fewer lymphoid cells in the cortex than in the medulla. In the spleen the white pulp is reduced and lymphoid cells from periarteriolar zones and at the chords are almost absent. In lymph nodes cortical small lymphocytes are depleted and primary and secondary nodules and germinal centers all but disappear. Cytotoxicity of lymphocytes is reduced by 86.2% in the thymus, 77.6% in the spleen and 70.2% in lymph nodes. The critical area of lesion is at the medialmost portion of the medial forebrain bundle, at the preoptic area and rostral part of the anterior hypothalamus. We suggest that this area contains neural circuits that are crucial for keeping the structure of lymphoid organs and the functional integrity of the immune system.

Mononuclear cell cytotoxicity in rats with Walker 256 tumor.

In the present study we characterized the cytotoxicity of Wistar rat mononuclear cells from 21 animals which received 10(6) Walker 256 tumor cells by the subcutaneous route. All animals developed the tumor. Cytotoxicity was studied 15 days after inoculation using spleen, thymus and lymph node T lymphocytes as well as macrophages from the peritoneal cavity. A Walker 256 tumor cell suspension and tumor cells in culture (YAC-1) were labelled with 51Cr and used as target cells, according to the Herberman technique and a gamma counter was used for counting. Anti-Walker cell cytotoxicity was significantly decreased in T lymphocytes from the spleen (9.6% vs 51.1% for the control) and thymus (11.5% vs 38.2% for the control), whereas no difference was observed for lymph nodes (41.2% vs 49.5% for the control) or macrophages (43.4% vs 46.3% for the control). Anti-YAC-1 cytotoxicity was significantly decreased in T lymphocytes from all lymphoid organs compared to control: 23.6% vs 42.8% for the spleen, 22.6% vs 41.1% for the thymus, 26.6% vs 42.1% for lymph nodes, and 27.1% vs 46.3% for macrophages. No correlation was observed between tumor weight, and anti-Walker cytotoxicity or anti-YAC-1 cytotoxicity.

Mononuclear cell cytotoxicity in rats with Walker 256 tumor

In the present study we characterized the cytotoxicity of Wistar rat mononuclear cells from 21 animals which received 10(6) Walker 256 tumor cells by the subcutaneous route. All animals developed the tumor. Cytotoxicity was studied 15 days after inoculation using spleen, thymus and lymph node T lymphocytes as well as macrophages from the peritoneal cavity. A Walker 256 tumor cell suspension and tumor cells in culture (YAC-1) were labelled with 51Cr and used as target cells, according to the Herberman technique and a gamma counter was used for counting. Anti-Walker cell cytotoxicity was significantly decreased in T lymphocytes from the spleen (9.6 vs 51.1 for the control) and thymus (11.5 vs 38.2 for the control), whereas no difference was observed for lymph nodes (41.2 vs 49.5 for the control) or macrophages (43.4 vs 46.3 for the control). Anti-YAC-1 cytotoxicity was significantly decreased in T lymphocytes from all lymphoid organs compared to control: 23.6 vs 42.8 for the spleen, 22.6 vs 41.1 for the thymus, 26.6 vs 42.1 for lymph nodes, and 27.1 vs 46.3 for macrophages. No correlation was observed between tumor weight, and anti-Walker cytotoxicity or anti-YAC-1 cytotoxicity.

Granulocytic sarcoma of the ovary in a nonleukemic patient.

We report a case of granulocytic sarcoma of the ovary preceding acute myeloid leukemia by twelve months, with no evidence of any hematological involvement at the time of first diagnosis. The patient was initially treated with surgery and chemotherapy for undifferentiated lymphoma and, although this aggressive protocol resulted in a complete response, granulocytic sarcoma recurred as extramedullary disease, followed by the appearance of acute myeloid leukemia. We discuss the clinical, histopathological and immunohistochemical features of the disease, the differential diagnosis and, in particular, the role of early aggressive treatment on the outcome of the patient.

[Acute myeloid leukemia after treatment of Hodgkin's disease]. / Leucemia mielóide aguda após tratamento da doença de Hodgkin.

The development of acute leukemia, particularly acute myeloid leukemia, represents a serious complication in patients treated with radio and/or chemotherapy for Hodgkin's disease. It has been reported with increasing frequency in the last years. Two such cases, that occurred in 87 patients treated for Hodgkin's disease, are reported. Complete autopsy was performed in both. The patients were less than 30 years old, received combined therapy during a prolonged time (more than 12 months), with an interval superior to 44 months between the diagnosis of Hodgkin's disease and the appearance of acute myeloid leukemia. The survival time was less than 12 months. Residual Hodgkin's disease was not observed.

[Renal insufficiency due to lymphomatous infiltration of the kidney: report of 3 cases and review of the literature]. / Insuficiência renal por infiltração linfomatosa dos rins: relato de três casos e revisão da literatura.

Renal failure in patients with lymphoma or leukemia may be brought about by different causes, including ureteral obstruction, hypercalcemia, hyperuricemia, amyloidosis, immunologically mediated nephrosis and paraproteinemic nephropathy. Lymphomatous or leukemic infiltration of the kidneys is a frequent finding at autopsy but is rarely seen as a cause of renal failure. In this report three patients with lymphomatous infiltration of the kidneys causing renal failure are described. Clinical and laboratory criteria for establishment of diagnosis in such cases are suggested. Using these diagnostic criteria, a renal biopsy may not be necessary.

Glucocorticoid receptors in acute leukemia.

We evaluated the applicability of glucocorticoid receptor (GR) determinations to predict clinical responsiveness to polychemotherapy in acute leukemias by measuring GR in leukemic cells from 20 patients as well as in lymphocytes from 20 normal volunteers. The whole-cell binding assay with [3H]-dexamethasone was used. The GR level (mean +/- SD) was 4583 +/- 1384 sites/cell (range: 2050-8140) for normal lymphocytes. A significant amount of GR (5300 to 17,000 sites/cell) was detected in the blasts from 9/12 patients with acute lymphoblastic leukemia (ALL). The concentration of GR sites in ALL cells greatly exceeded that found in normal mononuclear cells (P less than 0.01). The absence of GR in ALL patients correlated with poor response to polychemotherapy including glucocorticoids. High receptor levels were associated with complete remission (P less than 0.005). The GR concentration (7288 +/- 2345 sites/cell) found in acute non-lymphoblastic leukemias (ANLL) was in the same range as that found in ALL cases. All ANLL patients had a substantial number of GR, significantly higher than the sites/cell found in normal lymphocytes (P less than 0.05). No correlation between clinical responsiveness and receptor level was demonstrable for ANLL patients.

Sarcoma granulocitico (cloroma): compressao de medula espinal e envolvimento testicular. / Granulocytic sarcoma (chloroma): spinal cord compression and testicular involvement

Sao apresentados dois casos de sarcoma granulocitico (cloroma) com compressao de medula espinal, um deles com massa tumoral do testiculo. A revisao da literatura mostra que embora que embora a infiltracao microscopia do testiculo na leucemia mieloide seja frequente, massas tumorais sao raramente observadas. Os dois casos apresentados foram diagnosticados durante o curso de leucemia mieloide aguda. Os autores enfatizam a necessidade de identificacao da doenca na fase pre-leucemica quando o diagnostico histopatologico pode apresentar dificuldade sem o uso de coloracoes especificas

Aspergilose pulmonar, aspectos anatomo-patologicos de um paciente portador de leucemia linfoide aguda. / Pulmonary aspergillosis, anatomo-pathological aspects of a patient with acute lymphoid leukemia

Este e o relato de um caso de um paciente com leucemia linfoide aguda em tratamento que desenvolveu uma pneumonia necrotizante bilateral por Aspergillus sp. Os autores comentam o aumento da incidencia de infeccoes oportunistas principalmente em pacientes portadores de neoplasias malignas particularmente linfomas e leucemias

Epstein-Barr virus infections in Brazil. II. Hodgkin's disease.

Sixty-seven cases of Hodgkin's disease (HD) occurring in São Paulo, Brazil, were studied. Males with HD predominated over females 2.3 to 1. Sixty-six percent of the cases occurred in patients under 30 years of age, 31.7% under 20 years of age, and only 7.5% after 50 years of age. Lymphocyte predominance and mixed cellularity histologic types were most common in patients less than 15 years old, and nodular sclerosis was most common in the 15- to 19-year-old group. Sera from all patients had antibody to the viral capsid antigen (VCA) of Epstein-Barr virus (EBV). The geometric mean titer (GMT) of VCA antibody with the use of Jijoye cells as antigen was 1:162, and 31.3% of patients had titers of 1:320 or more; in controls, the GMT was 1:67 and 3.8% had titers of 1:320 or more. Similar results were obtained when EB-3 cells were used as antigen. The highest titers occurred in males, in mixed cellularity and lymphocyte depletion forms, and in stage 2 of illness. EBV-specific IgM antibody and heterophile antibody levels were not elevated, but 20.5% of the HD patients had antibody to the early antigen of EBV present in their sera. Antibody levels for herpes simplex virus, cytomegalovirus, rubella, measles, parainfluenza viruses, and papovavirus were not significantly elevated over those in matched controls.