Terapia alvo com mesilato de imatinibe : um estudo de 98 pacientes com leucemia mielóide crônica

Orientador: Ricardo PasquiniDissertaçao (mestrado) - Universidade Federal do Paraná, Setor de Ciencias da Saúde, Programa de Pós-Graduaçao em Medicina Interna. Defesa: Curitiba, 25/11/2005Inclui bibliografiaÁrea de concentraçao: Hematologi

Immune thrombocytopenia: clinical features and analysis of risk factors to response to the treatment

Introduction: Immune thrombocytopenia (ITP) is an acquired decrease of platelets, caused by autoantibodies against platelets, in the absence of an associated condition. ITP is associated to low morbidity and mortality, however there is reduced quality of life on the patients under treatment. This study has as objectives to describe the clinical features of the patients and the evaluation of risk factors related to the response to treatment. Methods: A retrospective analysis was achieved, regarding the medical records of 99 patients diagnosed with ITP and seen between May of 1992 and August of 2016 in a hospital.Results: 99 patients were analyzed, 71 female (71.7%). Mean age 39 years old to diagnosis (variation 2-84). 83.3% of the patients were chronic ITP and the mean follow up 49.2 months (0,1-289). 74.7% of patients presented bleeding to diagnosis. 76.7% of patients required treatment, and there was remission in 7 (30.4%) of the 23 patients who did not receive any treatment. 37 patients were submitted to splenectomy, 30 (81.1%) of those obtained partial or complete response and 18 (48.6%) presented loss of response. 30% of patients were submitted to posterior treatments. Only two patients had death related to ITP. In bivariate analysis of risk factors to response to the treatment, the only predictors of chronicity were initially the absence of corticosteroid dependence and absence of response to splenectomy, however in multivariate analysis those factors had their significance discarded. Conclusion: The presented results did not confirm a higher progression rate to chronicity in non corticosteroid-dependent patients and in those who did not present response to splenectomy. The clinical features, response pattern and survival of analyzed patients were similar to other studies reported.&nbsp

CAN NLR BE A BIOMARKER FOR MUCOSITIS AND GVHD IN PATIENTS UNDERGOING ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANTATION?

Allogeneic hematopoietic stem cell transplantation (HSCT) is the treatment for many diseases, however can induce important complications such as Oral Mucositis (OM) and Graft-versus-Host Disease (GVHD). The neutrophil-lymphocyte ratio (NLR) is a peripheral biomarker of systemic inflammation and an independent prognostic factor in several inflammatory diseases. Objective: The aim of this study was to evaluate the association of NLR with OM and GVHD in patients undergoing allogeneic HSCT. Methods: Patients who underwent  allogeneic HSCT at the Bone Marrow Transplant Service at the Hospital de Clínicas Complex of the Federal University of Paraná were included in the study. Sociodemographic data and blood count were collected from patients' medical records. NLR was calculated and associated with OM and GVHD. Results: 45 patients were included in the study. NLR was considerably higher in patients who had OM and oral GVHD when compared to patients who did not present these conditions, nonetheless no statistically significant difference was observed. Conclusion: Although both OM and GVHD are associated with inflammatory response as well as to the immune system, it was not associated with NLR. A further investigation considering other variables related to the HSCT might find possible association as it could favor patients management and prevention

Terapia alvo com mesilato de imatinibe : um estudo de 98 pacientes com leucemia mielóide crônica

Orientador: Ricardo PasquiniDissertaçao (mestrado) - Universidade Federal do Paraná, Setor de Ciencias da Saúde, Programa de Pós-Graduaçao em Medicina Interna. Defesa: Curitiba, 25/11/2005Inclui bibliografiaÁrea de concentraçao: Hematologi

Oral cancer after prolonged immunosuppression for multiorgan chronic graft-versus-host disease

Long-term survivors of hematopoietic stem cell transplantation are recognized as a risk group for malignization. Malignant oral neoplasms are increasingly being reported in the literature as a consequence of lesions of chronic graft-versus-host disease, and prolonged multidrug treatment to control its manifestations. This report describes a 43-year-old patient who, after allogeneic bone marrow transplantation, developed an oral squamous cell carcinoma secondary to the use of azathioprine, cyclosporine, prednisone, and tacrolimus, associated with multiorgan chronic graft-versus-host disease involving the oral mucosa, skin, eyes, and liver. This report aims to discuss the possible role of immunosuppressant therapy for chronic graft-versus-host disease on the development of oral squamous cell carcinoma, and the relevance of a close oral follow-up of patients to detect dysplastic or malignant alterations at an early stage

Molecular response to imatinib mesylate of Brazilian patients with chronic myeloid leukemia

Abstract Background Imatinib mesylate has revolutionized the treatment of chronic myeloid leukemia leading to significant reductions of BCR-ABL1 transcript levels in peripheral blood. Objective To evaluate the response to imatinib mesylate treatment (400 mg/day) in Brazilian patients in the chronic phase of chronic myeloid leukemia monitored by quantitative real time polymerase chain reaction. Methods Between October 2002 and October 2010, 3169 peripheral blood samples were collected from 1403 patients from 3 to 5 months, 6 to 11 months, 12 to 17 months, 18 to 23 months and ≥24 months after beginning imatinib treatment. Eighty-two patients had samples available and analyzed for all time intervals. BCR-ABL1 quantification was performed by quantitative real time polymerase chain reaction using the ABL1 gene as the control. Results of the BCR-ABL1 ratio as a percentage were reported by the international scale (IS) using the laboratory conversion factor (0.51). Results In the first interval, 80.8% of patients achieved the optimal response (BCR-ABL1 IS ≤ 10%). In the second period, 69.1% achieved optimal response (BCR-ABL1 IS ≤ 1%) and, between 12 and 17 months, 47.3% achieved major molecular response (BCR-ABL1 IS ≤ 0.1%). Conclusions The results of this retrospective study show that the response to imatinib treatment (400 mg/day) of Brazilian patients in the chronic phase of chronic myeloid leukemia is within the expected profile when compared to patients reported in international prospective randomized studies

Pre-sarcopenia and bone mineral density in adults submitted to hematopoietic stem cell transplantation

Abstract Background: The aim of this study was to evaluate the prevalence of pre-sarcopenia and bone mineral density after hematopoietic stem cell transplantation. Methods: The study group consisted of over 18-year-old patients who had been submitted to allogeneic transplantation at least one year previously. Patients and healthy controls were matched by sex, ethnic background, age, and body mass index. Body composition and bone mineral density were measured by dual-energy X-ray absorptiometry. A 24-h food recall and food frequency survey were performed. The biochemical evaluation included calcium, parathormone and vitamin D. Eighty-seven patients (52 men; age: 37.2 ± 12.7 years; body mass index: 25 ± 4.5 kg/m2) were compared to 68 controls [31 men; age 35.4 ± 15.5 years (p = 0.467); body mass index 25.05 ± 3.7 kg/m2 (p = 0.927)]. Results: There was no significant difference in the dietary intake between patients and controls. The mean levels of vitamin D were 23.5 ± 10.3 ng/mL; 29 patients (41.0%) had insufficient and 26 (37.14%) deficient levels. A higher prevalence of reduced bone mineral density was observed in 24 patients (25%) compared to 12 controls (19.1% - p < 0.001). Pre-sarcopenia was diagnosed in 14 (14.4%) patients and none of the controls (p = 0.05). There was a higher prevalence of pre-sarcopenia (66%) in patients with grades III and IV compared to those with grades 0-II graft-versus-host disease (10.9%) (p = 0.004). Conclusion: patients submitted to transplantation had a higher prevalence of pre-sarcopenia and greater changes in bone mineral density compared to controls; the severity of graft-versus-host disease had an impact on the prevalence of pre-sarcopenia

Unrelated hematopoietic stem cell transplantation in the pediatric population: single institution experience

OBJECTIVE: Hematopoietic stem cell transplantation has been successfully used to treat the pediatric population with malignant and non-malignant hematological diseases. This paper reports the results up to 180 days after the procedure of all unrelated hematopoietic stem cell transplantations in pediatric patients that were performed in one institution.METHODS: A retrospective review was performed of all under 18-year-old patients who received unrelated transplantations between 1995 and 2009. Data were analyzed using the log-rank test, Cox stepwise model, Kaplan-Meier method, Fine and Gray model and Fisher's exact test.RESULTS: This study included 118 patients (46.8%) who received bone marrow and 134 (53.2%) who received umbilical cord blood transplants. Engraftment occurred in 89.47% of the patients that received bone marrow and 65.83% of those that received umbilical cord blood (p-value < 0.001). Both neutrophil and platelet engraftments were faster in the bone marrow group. Acute graft-versus-host disease occurred in 48.6% of the patients without statistically significant differences between the two groups (p-value = 0.653). Chronic graft-versus-host disease occurred in 9.2% of the patients with a higher incidence in the bone marrow group (p-value = 0.007). Relapse occurred in 24% of the 96 patients with malignant disease with 2-year cumulative incidences of 45% in the bone marrow group and 25% in the umbilical cord blood group (p-value = 0.117). Five-year overall survival was 47%, with an average survival time of 1207 days, and no significant differences between the groups (p-value = 0.4666).CONCLUSION: Despite delayed engraftment in the umbilical cord blood group, graft-versus-host disease, relapse and survival were similar in both groups

Mutations in the breakpoint cluster region-Abelson murine leukemia 1 gene in Brazilian patients with chronic myeloid leukemia

Introduction: Mutations in the breakpoint cluster region-Abelson murine leukemia 1 gene are the leading cause of resistance to treatment with tyrosine kinase inhibitors in chronic myeloid leukemia patients. Mutations have been detected throughout the extension of the kinase domain of this gene and it is important to investigate their positions because there may be a difference in clinical relevance. Objective: To evaluate mutations in the transcripts of the BCR-ABL1 gene in Brazilian patients with chronic myeloid leukemia under tyrosine kinase inhibitor treatment in the Hospital de Clínicas of the Universidade Federal do Paraná. Methods: This retrospective observational cross-sectional study analyzed mutation data of BCR-ABL1 gene transcripts. Three hundred and thirty peripheral blood samples from 193 patients were evaluated with the search for mutations being achieved by Sanger sequencing. Results: Sixteen mutation types were identified in 48/193 (24.87%) patients with T315I (20.83%) being the most common. Furthermore, four polymorphisms (T240T, K247R, E275E and Y275Y) were identified. The highest incidence of mutations (19/53: 35.85%) occurred in the P-loop of the tyrosine kinase domain, whereas no mutation was found in the A-loop. In 43/48 (89.58%) patients only one mutation was found and more than one mutation was found in 5/48 (10.42%). The simultaneous presence of two mutations (E189G/V299L and E255K/T315I) was observed in 2/5 patients while the different mutations were seen in sequential samples of the other three patients (Y253Y/T315I, T315I/E255K and E255K/T315I). Conclusions: This molecular characterization contributed to the identification of the resistance profile to tyrosine kinase inhibitors in Brazilian patients, thus enabling the use of adequate therapeutic strategies in a timely manner. Keywords: Chronic myeloid leukemia, BCR-ABL1 gene, Mutation, Tyrosine kinase inhibitors, Resistanc