Polyostotic eosinophilic granuloma of the jaws treated by chemotherapy. A case report.

Eosinophilic granuloma is classified as a Langerhans cell histiocytosis. Although considered a rare pathology, up to 20% of all cases occur in the jaw bones, and radiographically may mimic odontogenic cysts or benign and malignant tumours. Different protocols have been suggested in the literature for treating eosinophilic granuloma. We report a case of polyostotic eosinophilic granuloma in a 34-year-old man showing ill defined mandibular and palatal radiolucencies. Due to the presence of multiple jaw lesions the treatment choice was chemotherapy. The clinical and radiographic feature are described, as well as treatment, complications and patient's follow-up.

Engraftment syndrome following autologous hematopoietic stem cell transplantation: definition of diagnostic criteria.

Engraftment syndrome (ES) is an increasingly reported complication of hematopoietic stem cell transplantation (HSCT). In order to better characterize the clinical criteria for the diagnosis of ES, we retrospectively analyzed 125 autologous HSCT recipients. ES was first defined as the presence of noninfectious fever plus skin rash. Patients with and without these findings were compared (univariate and multivariate analyses) regarding the presence of weight gain, hypoalbuminemia, pulmonary infiltrates, diarrhea, neurological manifestations and jaundice. The variables that are significantly more frequent in patients with fever and skin rash were incorporated in the definition criteria. The final diagnostic criteria were noninfectious fever plus any of the following: skin rash, pulmonary infiltrates or diarrhea. The incidence of ES was 20%. The single risk factor for ES by multivariate analysis was a diagnosis other than Hodgkin's disease (odds ratio 6.17, 95% confidence interval 1.38-27.78). Patients with ES received empirical antifungal therapy more frequently than patients without the syndrome (40 vs 19%, P=0.03), and had a longer duration of hospitalization (P=0.0007). The prospective application of these diagnostic criteria may have a favorable impact on the early diagnosis of the syndrome, with the initiation of corticosteroids and a reduction in the unnecessary use of antimicrobial agents.

Application of the IDSA guidelines for the use of antimicrobial agents in neutropenic patients: impact on reducing the use of glycopeptides.

We evaluated the impact of applying the Infectious Diseases Society of America guidelines for febrile neutropenic patients in reducing the use of glycopeptides. Forty-five prior episodes of febrile neutropenia were compared to 97 episodes seen after application of the guidelines. Glycopeptide use was reduced from 73% to 43% of episodes (P=.0008), without changes in outcome.

The value of an immunoenzymatic test (enzyme-linked immunosorbent assay) for the diagnosis of strongyloidiasis in patients immunosuppressed by hematologic malignancies.

The diagnosis of strongyloidiasis relies upon the identification of the parasite in stool samples. In 1981, a serologic assay was developed, which was useful in the diagnosis of strongyloidiasis in the immunocompetent host. In the present study, we evaluated the enzyme-linked immunosorbent assay (ELISA) in patients with hematologic malignancies. Between April 1995 and December 1998, sera from 164 consecutive patients were tested for the presence of IgG antibody to Strongyloides stercoralis. Patient was considered uninfected after at least three negative stool examinations. The prevalence of strongyloidiasis was 13%. The underlying diseases were acute leukemia in 21% and lymphoma in 52% of the patients. The majority of the patients were receiving chemotherapy (93%) and steroids (76%). The sensitivity, specificity, and positive and negative predictive values were 68%, 89%, 48%, and 95%, respectively. The ELISA may be an excellent assay to rule out the diagnosis of strongyloidiasis in patients with hematologic malignancies.

Predictive value of a positive nasal swab for Aspergillus sp. in the diagnosis of invasive aspergillosis in adult neutropenic cancer patients.

To evaluate the value of a positive nasal swab for Aspergillus in the diagnosis of invasive aspergillosis, we prospectively evaluated nasal colonization in 173 episodes of neutropenia in 92 patients with hematological malignancies. Weekly nasal swabs were taken, and the patients were followed until death or resolution of neutropenia. The outcome variables were the development of invasive aspergillosis, empirical antifungal therapy and death. In 31 episodes of neutropenia (18%) there was at least one positive nasal swab for Aspergillus sp. Only two patients developed invasive aspergillosis, both with a positive nasal swab (p = 0.03). The positive and negative predictive values of a nasal swab were 6.4% and 100%, respectively. There was no difference between patients with positive or negative swabs regarding antifungal therapy or death. In this population of patients, a nasal swab for Aspergillus sp. had a low positive predictive value and a high negative predictive value for invasive aspergillosis.

Clinical factors predictive of bone marrow involvement in Hodgkin's disease.

The role of bone marrow biopsy in the staging of Hodgkin's disease is undergoing reevaluation. We have studied the relationship of clinical factors to the presence of bone marrow involvement in 130 previously untreated patients with Hodgkin's disease. The presence of fever, spleen enlargement, anemia, leukopenia, poor performance status and poor histologic subgroups were positively correlated with the presence of bone marrow involvement in the univariate analysis. In the multivariate analysis, only fever, spleen involvement, leukopenia and poor histologic subgroups were significant. The predictive value of the absence of fever in regard to the absence of bone marrow involvement was 98%. The likelihood of bone marrow involvement in the absence of all four significant factors was only 0.05%. Patients without these clinical factors should probably not be submitted to a bone marrow biopsy as part of the staging procedures performed in Hodgkin's disease.

Antibiotic regimen as an independent risk factor for disseminated fungal infections in neutropenic patients in Brazil.

In a cohort of 79 febrile episodes in 50 consecutive neutropenic patients seen at the University Hospital, Federal University of Rio de Janeiro, Brazil, between 1987 and 1991, it was observed that the cumulative incidence of disseminated fungal infections rose from 3% to 19% after the introduction of a new empirical antibiotic regimen. In order to identify risk factors, as well as to assess the impact of the new antibiotic regimen on the emergence of fungal infections, a nested case-control study was undertaken, in which 10 cases of disseminated fungal infections were compared with 30 randomly chosen controls, drawn from the same cohort. In a multiple logistic regression analysis, the predictive factors for disseminated fungal infection were younger age (odds ratio 0.85, 95% confidence interval 0.75-0.97) and use of the new antibiotic regimen (odds ratio 14.18, 95% confidence interval 1.05-191.80) The probable explanation for the emergence of fungal infections is that the new antibiotic regimen, by lowering the incidence of bacteraemia-related deaths, allowed patients to be at risk for the development of disseminated fungal infections.

Tumor-growth and drug-resistance - lessons from the treatment of hodgkins-disease (review).

The resistance of cancer cells to anti-neoplastic agents is a major attribute of malignancy. Kinetic drug resistance develops as the tumor burden increases, and is reversible when the cell mass can be reduced. Genetic drug resistance, in contrast, results in the acquisition of possibly irreversible resistance by random cell mutation. The latter mechanism, and one of its corollaries, that rapidly alternating drug regimens could prevent the advent of new resistant cell lines, have been the subject of many studies in the last decade. The endpoint to evaluate in such studies should be an increase in failure-free survival, since such prevention cannot have any influence in the complete remission rates. A review of the clinical trials in Hodgkin's disease suggests that failure-free survival rates are in fact improved with the alternating schedules. On the other hand, dose-intensification is presently under study as a means of overcoming kinetic drug resistance, thereby increasing the complete remission rates, and has recently proved effective in the prolongation of survival in different malignancies. Further understanding of the mechanisms of drug resistance and the prospective appraisal of the combination of both high-dose therapy and alternating drug treatments should result in a better outcome, mostly for patients with large tumor burdens or other high risk factors.

Nodular lymphocyte predominant Hodgkin's disease progressing to a large B-cell lymphoma without previous treatment.

The nodular form of lymphocyte predominance Hodgkin's disease presents particular clinical and biological features that have set it apart as a distinct clinicopathological entity. It has an indolent course with long-term survival despite frequent localized relapses, and a remarkable tendency to progress into a B-cell non-Hodgkin's lymphoma. Biological evidence strongly point to a B-cell proliferation from the start. We report the unique case of a patient with nodular lymphocyte predominant Hodgkin's disease in stage I who had all disease removed for diagnosis and did not receive fu;ther treatment. He relapsed in the same lymph node area twelve years later, and the biopsy was now consistent with a large B-cell lymphoma. The histopathological and immunophenotypic profiles clearly show the identity of the two lymph node proliferations. This phenomenon exemplifies the growing inter-relashionship between Hodgkin's disease and non-Hodgkin's lymphomas.

Quinolone prophylaxis in neutropenic patients - efficacy versus resistance.

To assess the efficacy of quinolones in the prophylaxis of infections in neutropenic patients with acute non-lymphocytic leukemia, and to evaluate the emergence of quinolone resistance in two University Hospitals in Brazil, we retrospectively compared 101 consecutive episodes of neutropenia managed with quinolone prophylaxis between 1989 and November 1993, and 26 previous episodes without prophylaxis, and reviewed the results of in vitro sensitivity of Gram-negative strains to quinolones in the same period. Prophylaxis with quinolones resulted in less episodes of bacteremias (21% vs. 69%, p=10(-7)), including Gram-negative bacteremias (6% vs. 38%, p=10(-5)), with no statistically significant difference in the death rate (18% vs. 31%, p=0.14, 95% confidence interval -6-32). The resistance of Gramnegative strains to quinolones rose from 7% to 18% between 1990 and 1993 (p=10(-5)). The resistance against ceftazidime and amikacin, the agents used in the empirical antibiotic therapy, increased in the same proportion as the quinolones. Given the limited benefit of quinolones as prophylaxis and the increasing number of quinolone-resistant Gram-negative strains observed in our hospitals, the use of quinolones as prophylaxis must be seriously questioned. A stricter control of the use of quinolones in these hospitals might decrease resistance.

Application of an adapted international prognostic index for aggressive non-Hodgkin's lymphomas: good discrimination and lower survival rates in Rio de Janeiro, Brazil.

Institutions that treat patients with lymphoma must know their local therapy results and adapt their treatment strategies accordingly. To allow the application of the international prognostic factor index (IPI) in institutions where some of the data necessary are not available, we devised an approach by which the missing data would not impair the applicability of the index. We also collapsed the four categories of the IPI into two categories, and applied this adapted IPI to patients with aggressive non-Hodgkin's lymphoma treated in a public university hospital. Among the 72 patients treated with combination chemotherapy regimens containing doxorubicin, the following outcomes were observed for low and high risk groups, respectively: complete remission rates were 62% and 45% (p=0.2), overall survival rates were 48% and 14% (p=0.0098) and failure-free survival rates were 44% and 17% (p=0.03). This adapted IPI was very effective in predicting the outcome in the patients studied. The survival rates observed in our population were substantially lower than the rates reported in the IPI study. Patient selection might have played an important role in this difference, although other factors related to the social and general health status of the patients treated need to be prospectively studied.

Risk factors for typhlitis.

A case-control study was undertaken to identify risk factors for typhlitis in patients with hematological malignancies. A data base file with a total of 410 episodes of fever and neutropenia in patients cared for between May 1987 and 1996 was reviewed. Typhlitis was defined as a symptom complex of fever, intense abdominal pain and tenderness in the presence of neutropenia. Five cases of typhlitis were identified. Three controls for every patient were randomly selected from the same cohort. Diarrhea and jaundice were more frequent in patients than in controls (p=0.03). The presence of mucositis, prolonged duration of profound neutropenia and idarubicin treatment proved to be risk factors for typhlitis.

Ceftazidime plus amikacin plus teicoplanin or vancomycin in the empirical antibiotic therapy in febrile neutropenic cancer patients.

A prospective randomized trial was performed to compare teicoplanin to vancomycin as part of the empirical antibiotic therapy of febrile neutropenic cancer patients. Fifty-three patients were randomized to receive ceftazidime (100 mg/kg daily every 8 h), amikacin (15 mg/kg daily every 8 h) and teicoplanin (6 mg/kg once a day) and 53 other patients received ceftazidime, amikacin (same dosages) and vancomycin (30 mg/kg/day every 6 h). In 99 evaluable episodes, the success rates were 54% for patients receiving teicoplanin and 52% for patients receiving vancomycin (p=0.76, 95% CI-18-23). The response rates were similar for patients with unexplained fever and for patients with documented infections. There were no differences in renal toxicity or cutaneous side effects between the two groups. The overall death rate was 18.9%, with 10 deaths in each group. The most important factor associated with death was the diagnosis of a fungal infection (p=0.001). Teicoplanin seems to be well tolerated and as effective as vancomycin in the empirical antibiotic therapy of fever in neutropenic cancer patients.

Detection of messenger RNA in leukocytes or plasma of patients with chronic myeloid leukemia.

We investigated the presence of free mRNA in the plasma of patients with chronic myeloid leukemia (CML), through RT-PCR analysis of G3PDH, a metabolism gene. We also analysed the presence of mRNA for HLM, a human oxysterol-binding protein homologue recently described as a potential marker for blood dissemination of solid tumors. Our results showed the presence of metabolism G3PDH mRNA in the plasma of 5/11 (45%) CML patients studied but HLM mRNA was not detected in any of the plasma studied. HLM mRNA was detected in the leukocytes of 4/5 (80%) CML patients. This work reports for the first time free mRNA in the plasma of CML patients. Our results also suggest that the detection of HLM could be a potential molecular marker for the follow-up in hematological malignancies.

Fungal infections in neutropenic patients. A 8-year prospective study.

In this paper we report a eight-year prospective study designed to further characterize incidence, epidemiology, specific syndromes, treatment and prognosis associated with fungal infections in neutropenic patients. During the study period 30 fungal infections were diagnosed in 30 patients among 313 episodes of fever and neutropenia (10%). There were 15 cases of candidiasis, 5 pulmonary aspergillosis, 3 sinusitis by Aspergillus fumigatus, 5 infections by Fusarium sp., one infection by Trichosporon sp., and one infection due to Rhodotorula rubra. Blood cultures were positive in 18 cases (60%). The predisposing factors for fungal infection in multivariate analysis were the presence of central venous catheter (p < 0.001), longer duration of profound (< 100/mm3) neutropenia (p < 0.001), the use of corticosteroids (p < 0.001), gram-positive bacteremia (p = 0.002) and younger age (p = 0.03). In multivariate analysis only recovery of the neutropenia (p < 0.001) was associated with good prognosis whereas the diagnosis of infection by Fusarium sp. (p = 0.006) was strongly associated with a poor outcome. The death rate was 43%. There was no statistically significant difference in the death rate between patients who did receive (52%) or did not receive (50%) antifungal treatment. Identifying patients at risk, specific syndromes and prognostic factors may help to reduce the high mortality associated with disseminated fungal infections in neutropenic patients.

Characterization and analysis of the outcome of adults with acute myeloid leukemia treated in a Brazilian University hospital over three decades.

We evaluated the outcome of 227 patients with acute myeloid leukemia during three decades (period 1 - 1980's, N = 89; period 2 - 1990's, N = 73; period 3 - 2000's, N = 65) at a single institution. Major differences between the three groups included a higher median age, rates of multilineage dysplasia and co-morbidities, and a lower rate of clinical manifestations of advanced leukemia in recent years. The proportion of patients who received induction remission chemotherapy was 66, 75, and 85% for periods 1, 2, and 3, respectively (P = 0.04). The median survival was 40, 77, and 112 days, and the 5-year overall survival was 7, 13, and 22%, respectively (P = 0.01). The median disease-free survival was 266, 278, and 386 days (P = 0.049). Survival expectation for patients with acute myeloid leukemia has substantially improved during this 30-year period, due to a combination of lower tumor burden and a more efficient use of chemotherapy and supportive care.