Bacteremia caused by CDC group IV c-2 in a patient with acute leukemia.

Human infection due to CDC group IV c-2, a gram negative bacillous, are rare. We describe a case of nosocomial bacteremia caused by this organism in a neutropenic patient with acute lymphoblastic leukemia and include a literature review of CDC group IV c-2 infection in patients with hematologic malignancies

Fatal airway disease in an adult with chronic graft-versus-host disease

Chronic graft-versus-host disease (GVHD) is a syndrome of disordered immunity in which a variety of opportunistic respiratory infections have been documented. Restrictive pulmonary disease without advanced fibrotic changes has been also known to occur; obstructive lower airways disease related to chronic GVHD has apparently not been referred to. We report a patient with chronic GVHD and irreversible airways obstruction who died in respiratory failure caused by generalised bronchiolar damage progressing over a few months. Lung function studies showed severe airflow limitation and a leftward shift in the pressure-volume curve indicating a loss of elastic recoil pressure. Postmortem pulmonary lesions were consistent with a necrotising obliterative bron chiolitis. Our purpose is to describe this unusual complication not previously reported in chronic GVHD and discuss the pulmonary mechanics

A novel orally available inhibitor of focal adhesion signaling increases survival in a xenograft model of diffuse large B-cell lymphoma with central nervous system involvement

Central nervous system dissemination is a relatively uncommon but almost always fatal complication in diffuse large B-cell lymphoma patients. Optimal therapy for central nervous involvement in this malignancy has not been established. In this paper, we aimed to evaluate the therapeutic effect of E7123, a celecoxib derivative that inhibits focal adhesion signaling, in a novel xenograft model of diffuse large B-cell lymphoma with central nervous system involvement. Cells obtained after disaggregation of HT subcutaneous tumors (HT-SC cells) were intravenously injected in NOD/SCID mice. These mice received oral vehicle or 75 mg/kg of E7123 daily until they were euthanized for weight loss or signs of sickness. The antitumor effect of E7123 was validated in an independent experiment using a bioluminescent mouse model. Intravenously injected HT-SC cells showed higher take rate and higher central nervous system tropism (associated with increased expression of beta 1-integrin and p130Cas proteins) than HT cells. The oral administration of E7123 significantly increased survival time in 2 independent experiments using mice injected with unmodified or bioluminescent HT-SC cells. We have developed a new xenograft model of diffuse large B-cell lymphoma with central nervous system involvement that can be used in the pre-clinical evaluation of new drugs for this malignancy. E7123 is a new, well-tolerated and orally available therapeutic agent that merits further investigation since it may improve current management of diffuse large B-cell lymphoma patients with central nervous system involvement

IL-6 and IL-8 levels in plasma during hematopoietic progenotor transplant

Background and objective: the relationship between cytokine concentrations and transplant-related complications has been studied in bone marrow transplant patients. The changes in TNF-alpha, IL-1 and IL-6 concentrations after transplantation are well documented in the literature but this is not the case for IL-8. The purpose of the present study was to investigate prospectively the plasma concentration of these cytokines and their relationship to transplant-related complications. Design and methods: pro-inflammatory cytokine (TNF-alpha, IL-1, IL-6 and IL-8) levels in plasma were determined in a group of 53 patients undergoing hematopoietic progenitor transplantation. Plasma samples were collected weekly from day -7 to day +35 and stored at -70 degrees C until assayed by ELISA. The major transplant-related toxicities registered were: veno-occlusive disease (VOD), acute graft-versus-host disease (GVHD), infectious episodes, renal failure and mucositis. Results: in spite of the great variability of plasma cytokine profiles between the different patients, we came to various conclusions. Patients' TNF-alpha and IL-1 concentrations correlated well over time. IL-6 and IL-8 profiles were similar and correlated well with febrile episodes. In some cases, an increase in IL-6 preceded hematologic recovery. In our study, increased levels of TNF-alpha, IL-6 and especially IL-8 correlated with hepatic or renal dysfunction as evaluated by increased bilirubin and creatinine in plasma, while pulmonary complications correlated only with increased IL-6 levels. Allogeneic transplant patients had a tendency to have higher TNF-alpha concentrations than autologous transplant patients, probably because an allogeneic transplant is associated with more transplant-related toxicity. Basal disease usually had no effect on cytokine profiles. Interpretation and conclusions: IL-6 and IL-8 were the only cytokines studied whose increase correlated with febrile episodes. High IL-8 values may be a useful predictor of renal dysfunction and pulmonary disease and seems to trigger off high IL-6 levels. Plasma TNF-alpha and IL-1 concentrations during the posttransplant period have not been shown to be predictive of the development of transplant-related complications, and none of the profiles was recognized to be specific for a particular complication in this study

Post-transplant lymphomas: a 20-year epidemiologic, clinical and pathologic study in a single center

Background and objectives: to study the incidence, clinical presentation, pathologic features and outcome of post-transplant lymphomas (PTL) during the past 20 years. Design and methods: we undertook a descriptive study of all biopsy-proven cases of PTL diagnosed in our hospital from 1979 through 1999. The average annual incidence rate of PTL was analyzed at 5-year intervals from 1979 to 1999. Risk ratios were estimated by comparing the incidence of PTL among transplanted patients with that of lymphoma observed in the general population of the region. Survival analysis was performed at the univariate level using the Kaplan Meier technique and at the multivariate level by Cox hazard models. Results: seventeen of 1,860 transplanted patients developed a PTL (0.9%). The risk of PTL was calculated to be almost 8-fold higher than the risk of lymphoma in the general population. The risk was highest among those who had received a heart transplant (RR=35.6). The mean time between transplant and the diagnosis of PTL was 31 +/- 29 months. Of all PTL, 88% were of B-cell origin and 53% of the cases tested were Epstein-Barr virus (EBV)-positive. The median survival was 24 months. The majority of patients with allograft involvement died within the 2 months following diagnosis (hazard ratio 5.3; 95% CI 1.4-20.7). Interpretation and conclusions: organ transplantation is a major risk factor for the development of lymphoma, a disease with a particularly bad prognosis when it develops at the site of the allograft. Early diagnosis and more specific treatment may improve PTL survival

La inmunoteràpia en la leucèmia aguda

Clàssicament hom considerava que la relació hoste-tumor era una relació saprofítica a favor del tumor que creixia a l'interior del subjecte hoste, al qual utilitzava per a nodrir-se i al qual consumia en aquesta relació. Ja l'any 1905 Cohen observa que l'hoste participava activament en aquesta relació i que fins i tot la condicionava, en estudiar tumors en rates. En els seus experiments veié que..

La inmunoteràpia en la leucèmia aguda

Clàssicament hom considerava que la relació hoste-tumor era una relació saprofítica a favor del tumor que creixia a l'interior del subjecte hoste, al qual utilitzava per a nodrir-se i al qual consumia en aquesta relació. Ja l'any 1905 Cohen observa que l'hoste participava activament en aquesta relació i que fins i tot la condicionava, en estudiar tumors en rates. En els seus experiments veié que..

Early mortality in bone marrow transplantation for acute lymphocytic leukaemia a multivariate analysis of risk factors

Objectives: bone marrow transplantation is still associated with a high case-fatality rate. This study was conducted to identify the risk factors for early mortality in acute lymphocytic leukaemia patients treated with bone marrow transplantation. Methods: prospectively collected data on 76 acute lymphocytic leukaemia patients, treated with 60 mg/kg cyclophosphamide for two consecutive days, before (32 patients) or after (44 patients) total body irradiation who received an allogeneic (56 patients) or autologous (20 patients) bone marrow transplantation were considered in the multivariate analysis including fifteen potentially prognostic variables for early mortality. Results: in the entire group, patients older than 20 years had a relative risk for early mortality of 3.96 (95% confidence interval (CI): 1.33-11.76) and those with a Karnofsky Index lower than 90% had a relative risk of 5.56 (95% CI: 1.29-25). In the subgroup of allogeneic patients, those over 20 years had a relative risk of 5.17 (95% CI: 1.30-20.6); the relative risk for patients with a Karnofsky index < 90% was 10.55 (95% CI: 1.55-71.43) and 8.04 (95% CI: 43-45.07) for acute severe graft-versus-host disease. Among radiation therapy variables only dose-rate showed a trend towards better prognosis in patients treated with less than 5 cGy/min. Conclusions: in our patients and within the range of treatment variables studied, age, Karnofsky index, and graft-versus-host disease are the most important factors related with early mortality

Early mortality in bone marrow transplantation for acute lymphocytic leukaemia a multivariate analysis of risk factors

Objectives: bone marrow transplantation is still associated with a high case-fatality rate. This study was conducted to identify the risk factors for early mortality in acute lymphocytic leukaemia patients treated with bone marrow transplantation. Methods: prospectively collected data on 76 acute lymphocytic leukaemia patients, treated with 60 mg/kg cyclophosphamide for two consecutive days, before (32 patients) or after (44 patients) total body irradiation who received an allogeneic (56 patients) or autologous (20 patients) bone marrow transplantation were considered in the multivariate analysis including fifteen potentially prognostic variables for early mortality. Results: in the entire group, patients older than 20 years had a relative risk for early mortality of 3.96 (95% confidence interval (CI): 1.33-11.76) and those with a Karnofsky Index lower than 90% had a relative risk of 5.56 (95% CI: 1.29-25). In the subgroup of allogeneic patients, those over 20 years had a relative risk of 5.17 (95% CI: 1.30-20.6); the relative risk for patients with a Karnofsky index < 90% was 10.55 (95% CI: 1.55-71.43) and 8.04 (95% CI: 43-45.07) for acute severe graft-versus-host disease. Among radiation therapy variables only dose-rate showed a trend towards better prognosis in patients treated with less than 5 cGy/min. Conclusions: in our patients and within the range of treatment variables studied, age, Karnofsky index, and graft-versus-host disease are the most important factors related with early mortality

Evaluation and prevention of oral complications in patients subjected to bone marrow transplantation. A clinical study

Objetivo: Analizar la relación entre el grado de inflamación gingival de un grupo de pacientes trasplantados de médula ósea y el tipo de mucositis que presentan. Diseño: Se estudian 58 pacientes con enfermedad hematológica que son trasplantados de médula ósea. La población se clasifica en tres grupos: grupo A (pacientes vistos antes y después de la infusión), grupo B (pacientes explorados sólo después de la infusión) y grupo C (todos los pacientes vistos después de la infusión). Se realiza un protocolo de exploración antes, durante y después del tratamiento. Los resultados se procesan mediante el paquete estadístico SPSS+ Windows, realizándose un análisis descriptivo. Resultados: El CAOd registrado es de 10,7. El índice de sangrado antes de la infusión es del 10%, pasando al 15% post-infusión (22% si se considera el grupo C). El índice gingival pre-tratamiento es de 1,6 (grupo A), pasando a 1,3 post-trasplante y siendo de 1,9 para el grupo B. El índice de placa pasa de 1,8 a 1,4 en el grupo A y es de 2,1 en el grupo B. El 82% de los pacientes presentan mucositis de grado II, III ó IV. La correlación entre índice gingival mayor o menor de 1,5 y grado de mucositis presentado es estadísticamente significativa, con una p<0,000. Conclusiones: La visita previa al paciente que será transplantado implica un mejor índice gingival post-trasplante. El mayor grado de inflamación gingival conlleva un mayor grado de mucositis. Es importante controlar la inflamación gingival como medida para prevenir la mucositis