FREDERICO LUIZ DULLEY
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- Risk factor for death in hematopoietic stem cell transplantation: are biomarkers useful to foresee the prognosis in this population of patients?(2014) MASSARO, K. S. R.; MACEDO, R.; CASTRO, B. S. de; DULLEY, F.; OLIVEIRA, M. S.; YASUDA, M. A. S.; LEVIN, A. S.; COSTA, S. F.The morbidity and mortality in hematopoietic stem cell transplantation (HSCT) occur due to infectious complications and constitute the major clinical problems in HSCT recipients. The role of the use of biomarkers in post-HSCT patients is still controversial. To assess the serum values of biomarkers interleukin 6 (IL-6), procalcitonin (PCT) and C-reactive protein (CRP) and risk factors for post-HSCT death. Prospective study conducted in patients submitted to HSCT at a university hospital. Biomarkers (IL-6, PCT and CRP) were assessed on the day afebrile neutropenia was detected, in the febrile event, 24 and 72 h after fever onset and 48 h or 5 days if fever persisted. Patients were compared as to the death outcome within 30 days from the HSCT. Variables with p < 0.15 were included in the multivariate analysis model (MVA) that were performed for all patients included in the study and separated for autologous and allogeneic HSCT patients. 296 patients with ages ranging between 15 and 70 years, neutropenic, submitted to HSCT, being 216 (73 %) autologous and 80 (20 %) allogeneic were assessed. One hundred and ninety (64.2 %) patients presented fever after the transplantation and infection microbiologically controlled in 78 (26.4 %). Twenty-three cases (7.8 %) evolved to death. The risk factors associated with death in the bivariate analysis were age, allogeneic transplantation, unrelated transplantation, GVHD, bloodstream infection by Gram-negative, IL-6 > 140 pg/mL and CRP a parts per thousand yen120 mg/L and the protective ones were lymphoma and hospital outpatient support. The independent variables in the MVA associated with death were allogeneic and unrelated transplantation, blood stream infection (BSI) by Gram-negative, LDH a parts per thousand yen390 UI/L, urea a parts per thousand yen25 mg/dL and CRP a parts per thousand yen120 mg/L for HSCT transplanted patients and BSI due to Gram-negative and CRP a parts per thousand yen120 mg/L for allogeneic HSCT, however, CRP a parts per thousand yen120 mg/L did not remain in the model when urea a parts per thousand yen25 mg/L was included. No independent risk factor was found for autologous patients. Out of the biomarkers assessed, only CRP a parts per thousand yen120 mg/L was independently associated with death. Other risk factors found were: type of transplantation (allogeneic and unrelated), bloodstream infection by Gram-negative, LDH a parts per thousand yen390 UI/L and urea a parts per thousand yen25 mg/dL. For allogeneic patients only CRP a parts per thousand yen120 mg/L and BSI due to Gram-negative were risk factors for death; however, CRP did not remain in the model when urea a parts per thousand yen25 mg/L was included.
- Clusters of infection due to metallo-beta-lactamase-producing Pseudomonas aeruginosa in stem cell transplant and haematology units(2011) PAEZ, J.; LEVIN, A. S.; FU, L.; BASSO, M.; FONSECA, G. H. H.; DULLEY, F. L.; ROSSI, F.; GUIMARAES, T.; COSTA, S. F.
conferenceObject Oral leukoplakia in chronic graft versus host disease(2012) PAVESI, V. C. S.; FRANCA, C. M.; CASTELLI, J. B.; SABOYA, R.; DULLEY, F. L.; CORACIN, F. L.Introduction: Late complications of allogeneic hematopoietic stem cell transplantation (HSCT) include a risk of secondary malignancies and early diagnosis of oral premalignant or malignant lesions requires an assessment of potential predisposing risk factors. Patients with oral epithelial dysplasia after allogeneic HSCT include oral cGVHD as a potential risk factor for oral cancer. A better understanding of the clinical features and potential factors associated with secondary oral cancer, may be benefit predicting and identifying this late complication of allogeneic HSCT. Case details: A 37 years old male who had received an allogeneic hematopoietic stem cell transplantation in October/2002 was referred to a Oral Medicine Outpatient in August 2011 with a white-plaque lesion of the oral mucosa the conditioning regimen to HSCT comprised busulfan-melphalan and graft-versus-host disease prophylaxis was cyclosporine-methotrexate. The patient developed lichenoid-oral cGVHD around day 60 and treatment comprised corticosteroid-cyclosporine. Clinical examination revealeda non-symptomatic 2 cm white-plaque of the hard palate. Exfoliative cytology was performed and no atypical cells were seen. The lesion increased in size to 4 cm long during the next 10-days. An incisional biopsy was undertaken and histopathological analysis revealed an epithelial tissue with acanthosis, hypergranulosis, hyperkeratosis, papilomatosis and apoptosis plus lymphocyte exocitosis. No atypical, cell dysplasia or koylocites were present. Mild to moderate cGVHD activity was seen. In this case, the patient was monitored in our outpatient program and no changes were noted in the lesion. Conclusion: The associationbetweenchronic graftversus host disease andoralsquamous cell carcinoma suggests a close monitoring of patients for early diagnosis of possible secondaryneoplasmsanddemonstratestheaggressivebehaviourofthislatecomplication. Relevance: Due to this aggressive behaviour and the increase number of HSCT worldwide, careful long-term follow-up by a cancer team, including oral medicine expertise, is recommended, and patients should be aware of cancer risk.- Healthcare-associated infection in hematopoietic stem cell transplantation patients: risk factors and impact on outcome(2012) MENDES, Elisa Teixeira; DULLEY, Frederico; BASSO, Mariusa; BATISTA, Marjorie Vieira; CORACIN, Fabio; GUIMARAES, Thais; SHIKANAI-YASUDA, Maria Aparecida; LEVIN, Anna Sara; COSTA, Silvia FigueiredoObjective: The objective of this study was to analyze the incidence of and risk factors for healthcare-associated infections (HAI) among hematopoietic stem cell transplantation (HSCT) patients, and the impact of such infections on mortality during hospitalization. Methods: We conducted a 9-year (2001-2009) retrospective cohort study including patients submitted to HSCT at a reference center in Sao Paulo, Brazil. The incidence of HAI was calculated using days of neutropenia as the denominator. Data were analyzed using EpiInfo 3.5.1. Results: Over the 9-year period there were 429 neutropenic HSCT patients, with a total of 6816 days of neutropenia. Bloodstream infections (BSI) were the most frequent infection, presenting in 80 (18.6%) patients, with an incidence of 11.7 per 1000 days of neutropenia. Most bacteremia was due to Gram-negative bacteria: 43 (53.8%) cases were caused by Gram-negative species, while 33 (41.2%) were caused by Gram-positive species, and four (5%) by fungal species. Independent risk factors associated with HAI were prolonged neutropenia (odds ratio (OR) 1.07, 95% confidence interval (CI) 1.04-1.10) and duration of fever (OR 1.20, 95% CI 1.12-1.30). Risk factors associated with death in multivariate analyses were age (OR 1.02, 95% CI 1.01-1.43), being submitted to an allogeneic transplant (OR 3.08, 95% CI 1.68-5.56), a microbiologically documented infection (OR 2.96, 95% CI 1.87-4.6), invasive aspergillosis disease (OR 2.21, 95% CI 1.1-4.3), and acute leukemias (OR 2.24, 95% CI 1.3-3.6). Conclusions: BSI was the most frequent HAI, and there was a predominance of Gram-negative microorganisms. Independent risk factors associated with HAI were duration of neutropenia and fever, and the risk factors for a poor outcome were older age, type of transplant (allogeneic), the presence of a microbiologically documented infection, invasive aspergillosis, and acute leukemia. Further prospective studies with larger numbers of patients may confirm the role of these risk factors for a poor clinical outcome and death in this transplant population. (C) 2012 Published by Elsevier Ltd on behalf of International Society for Infectious Diseases.
conferenceObject Patients oral conditions before hematopoietic stem-cell transplantation in Brazil(2012) CORACIN, F. L.; SOARES JUNIOR, L. A. V.; DULLEY, F. L.; SABOYA, R.; SILVA-SANTOS, P. S. da; TINOCO-ARAUJO, J. E.; COLTURATO, V. A. R.; ANTUNES, H. S.; FERREIRA, C. G.; BOUZAS, L. F. S.; PEREIRA, S. C. M.; MONTEIRO, M. C. P.; RAMPINI, M. P.; MAYHE, R.; LIME, E. M.; TANIMOTO, H. M.; PATON, E. J. A.; SILVA, G. B. L.; SACONO, N. T.; BATISTA, A. C.; BARIANI, C.; PERES, M. P. S. M.Objectives: This prospective multicenter study aims to conduct an epidemiologic survey of oral health status of the patients waiting for the hematopoietic stem cell transplantation (HSCT) in five Brazilian Centers to identify oral needs prior to HSCT. Methods: Patients enrolled in this study were submitted to a dental clinical evaluation whilst they were awaiting for HSCT, performed by a dentist from the participating Institution. Demographic and medical data were collated together with, gingival (GI) and plaque (PI) indexes and index of decay missed and filled teeth (DMFT) were evaluated. These indexes are indicators of oral health according to the World Health Organization (WHO). Results: During the period between April 2011 and April 2012, 101 (73 male and 48 female) patients were enrolled in this prospective study at five HSCT Brazilian Centers. Underlying diseases comprised 25 multiple myeloma, 24 non-Hodgkin lymphoma, 19 acute lymphoblastic leukemia, 16 acute myelogenous leukemia, 13 severe aplastic anemia, 11 Hodgkin lymphoma, six chronic myelogenous leukemia, three myelodisplastic syndrome, one testicular tumor, one retinoblastoma, one myelofibrosis and one chronic lymphoblastic leukemia. Median age was 40 years (range: 4–67). At the time of the survey, patients presented mean GI = 0.8, mean PI = 1.2. DMFT index were evaluated in 104/121 patients and showed mean of 16.1. Conclusion: Patients undergoing HSCT need comprehensive oral care in Brazil due a poor oral health at the time of transplantation, to avoid possible infections secondary to myelosuppression and mucosal barrier injury. Relevance: The patients’ status prior-HSCT may to lead to protocols of dental treatment before HSCT suggesting an important role in the maintenance of oral integrity. Prior dental intervention can lead a better quality of life and improve the results of transplantation, reducing time of mucositis and infections.- An outbreak of respiratory syncytial virus infection in hematopoietic stem cell transplantation outpatients: good outcome without specific antiviral treatment(2013) MENDES, E. T.; RAMOS, J.; PEIXOTO, D.; DULLEY, F.; ALVES, T.; BOAS, L. S. Vilas; BATISTA, M. V.; SILVA, D. P. da; LEVIN, A. S.; SHIKANAI-YASUDA, M. A.; COSTA, S. F.Background. Respiratory syncytial virus (RSV) is a common cause of seasonal respiratory viral infection in hematopoietic stem cell transplantations (HSCT) patients. The efficacy of treatment, however, remains controversial. We describe an outbreak of 31 cases of RSV that occurred in an HSCT outpatient care unit in the fall season from March through May 2010, with a good outcome without any specific antiviral treatment. Methods. During these 3 months, 222 nasal wash samples were tested and, of these, 31 outpatients were positive for RSV. In 2009, 99 samples had been tested and only 10 outpatients were positive for RSV in the same period. Results. Seven (22.5%) patients had severe neutropenia (<500 cells/mu L); severe lymphopenia (<200 cells/mu L) was present in 13 (41.9%) patients, and 14 (45%) had received intravenous broad-spectrum antibiotics. Hospitalization was necessary only for 8 patients (25.8%); 20 had lower respiratory tract infection (64.5%). Only 1 patient died as a result of proven invasive aspergillosis. Conclusion. This report suggests that HSCT outpatients with no risk factors may not always require specific treatment for RSV.
- Empiric use of linezolid in febrile hematology and hematopoietic stem cell transplantation patients colonized with vancomycin-resistant Enterococcus spp(2015) LISBOA, Luiz F.; MIRANDA, Bianca G.; VIEIRA, Marjorie B.; DULLEY, Frederico L.; FONSECA, Guilherme G.; GUIMARAES, Thais; LEVIN, Anna S.; SHIKANAI-YASUDA, Maria A.; COSTA, Silvia F.Objectives: We conducted a retrospective study on the impact of the empiric use of linezolid on mortality in vancomycin-resistant Enterococcus spp (VRE)-colonized hematology and hematopoietic stem cell transplantation (HSCT) patients. Methods: VRE-colonized inpatients for whom complete data were available (n = 100) were divided into two groups: those who received empiric linezolid in the course of fever refractory to broad-spectrum antibiotics, replacing the glycopeptide utilized for the previous 48 h, and those who did not (control group). All patients were followed until hospital discharge or death. The impact of linezolid and risk factors for all-cause mortality were evaluated; variables with p < 0.10 were analyzed in a multivariate model. A Kaplan-Meier survival analysis was done to compare survival among febrile patients colonized by VRE who received empiric linezolid with patients who did not receive linezolid. Results: Patients empirically prescribed linezolid were generally younger (median age 33 vs. 44 years; p = 0.008) and more likely to be recipients of an allogeneic HSCT (24 (68.6%) vs. 24 (36.9%); p = 0.009) than patients who did not receive the drug. Fourteen (21.5%) VRE bloodstream infections were diagnosed, all in patients who did not receive empiric linezolid (p = 0.002). In-hospital mortality was comparable in empiric linezolid and non-linezolid users (19 (54.3%) vs. 27 (41.5%), respectively; p = 0.293). The Kaplan-Meier survival analysis showed no significant difference in survival comparing the group that received linezolid to the group that did not (p = 0.72). Graft-versus-host disease (GVHD; odds ratio (OR) 5.90, 95% confidence interval (CI) 1.46-23.79; p = 0.012) and persistence of neutropenia (OR 6.93, 95% CI 1.72-27.94; p = 0.0065) were independent predictors of all-cause in-hospital death in HSCT patients, and persistence of neutropenia in non-HSCT patients (OR 8.12, 95% CI 1.22-53.8; p = 0.030). Conclusions: The empiric use of linezolid in VRE-colonized hematology patients had no impact on mortality, which appeared rather to be associated with the persistence of neutropenia in general and GVHD in the HSCT group. (C) 2015 The Authors.
conferenceObject Ciclosporine-induced fibrovascular polyps in the tongue(2012) TORRES-PEREIRA, C.; SABOYA, R.; CASTELLI, J. B.; ROCHA, A. C.; ROCHA, G. B. L.; BONFIM, C. S.; DULLEY, F. L.; CORACIN, F. L.Introduction: Cyclosporine (CsA) is used for chronic graft-versus-host disease (cGVHD) treatment and can lead to increased or synthesis of collagen and fibrous eposition. Gingival overgrowth is a common adverse effect of CsA, however it is rarely seen in patients using CsA for treatment of cGVHD. The development of CsA- associated nongingival growth is rare and represents polyps of granulation/fibrous tissue. These lesions have been referred as oral inflammatory polyps that may be aggravated in the presence of cGVHD. Case details: A 6 year old male with Fanconi Anemia underwent an unrelated hematopoietic stem-cell transplantation (HSCT) in March/2007. cGVHD was diagnosed in skin and oral mucosa and was treated with cyclosporine and corticosteroids. In August 2008 the patient was referred to the Oral Medicine Service for evaluation of a 3 cm growing polyps in the border of the tongue. Incisional biopsy was performed and revealed fibrous-vascular hyperplasia. While the patient waited for an excisional biopsy, the polyps increased in size to 10 cm. This biopsy revealed the same histopathological characteristic. In May 2011 the patient presented with other polyps of the middle side of tongue associated with other small nodules. These lesions were completely removed and again the diagnosis of fibrous-vascular hyperplasia was given immunohistochemistry examination revealed negativity to anti-cytomegalovirus (CMV)/anti-herpesvirus (HSV) and Ki-67 expression showed moderate to strong staining. No atypical cells were observed. Conclusions: Although it is an unusual reported lesion, fibrous-vascular polyps are a recent described pathological entity associated with the use of CsA. These lesions should be considered as a differential diagnosis of oral masses in post HSCT Fanconi Anemia patients, particularly to exclude malignancies in this high risk group of individuals. Relevance: Fanconi anaemia patients need to be closely monitored due to a high prevalence of secondary malignancies.- Impact of oral care prior to HSCT on the severity and clinical outcomes of oral mucositis(2011) SANTOS, Paulo Sergio da Silva; CORACIN, Fabio Luiz; BARROS, Jose Carlos de Almeida; DULLEY, Frederico Luiz; NUNES, Fabio Daumas; MAGALHAES, Marina GallottiniPatients who undergo hematopoietic stem cell transplantation (HSCT) frequently experience gastrointestinal toxicity as a result of their preparative regimen. The most frequent manifestation is oral mucositis (OM) and diarrhea. We studied the effects of oral care prior to HSCT on the severity of OM. Seventy patients suffering from hematologic malignancies who had undergone HSCT were divided into two groups (35 patients - Study Group [SG] and 35 - Control Group [CG]), and the severity of OM was evaluated by two calibrated dentists, using the WHO scale. The patients from the SG received oral care prior to HSCT and those from CG did not receive any dental care. The results showed no differences (p = 0.20) in the incidence or severity of OM among the groups. However, patients from the SG presented a shorter time elapsed (p < 0.001) when compared with the CG (median: 10 vs. 20 d). Our results show the importance of simple, inexpensive preventive intervention to control the time elapsed of OM, which reduces morbidity and, as a consequence, the cost of the treatment.
bookPart Transplante de células-tronco hematopoiéticas(2013) DULLEY, Frederico Luiz; SABOYA, Rosaura