Donor characteristics and hematopoietic stem cell transplantation outcome: experience of a single center in Southern Brazil.

BACKGROUND: Hematopoietic stem cell transplantation is a curative treatment for many patients with hematological disorders. Donor-recipient genetic disparity, especially involving the human leukocyte antigen system is a critical factor for transplant outcome. OBJECTIVE: To evaluate retrospectively donor characteristics and correlations with the occurrence of acute and chronic graft-versus-host disease, disease-free survival and overall survival in a Brazilian population submitted to allogeneic hematopoietic stem cell transplantation between 1994 and 2012 in a single center. RESULTS: Three hundred and forty-seven consecutive transplantations were included. Related transplants (81.2%) were significantly more common than unrelated transplants (18.7%); donor and recipient median ages were 34 (range: 1-61) and 33 (range: 3-65) years respectively with donor HLAs being matched for 333 (95.9%) patients. Donor gender, cytomegalovirus status and ABO incompatibility did not influence the five-year overall survival. In univariate analyses, overall survival was negatively influenced by the presence of acute graft-versus-host disease (33% vs. 47%, respectively; p-value = 0.04), unrelated transplant (41.5% vs. 50.9%, respectively; p-value = 0.045) and donors aged over 40 years (41% vs. 52%, respectively; p-value = 0.03). Older donors were associated with a higher rate of acute (52% vs. 65.8%; p-value = 0.03) and chronic graft-versus-host disease (60% vs. 43%, respectively; p-value = 0.015). In multivariate analyses, acute graft-versus-host disease [relative risk (RR): 1.8; 95% confidence interval (CI): 1.1-29; p-value = 0.008] and older donors (RR: 1.6; 95% CI 1.11-2.24; p-value = 0.013) were associated with higher transplant-related mortality. CONCLUSIONS: In transplant patients, to have a donor older than 40 years of age seems to significantly increase the incidence of acute and chronic graft-versus-host disease and transplant-related mortality with no impact on disease-free survival and overall survival. In spite of the rather small cohort of patients, these findings are similar to what is described in the literature suggesting that a younger donor should be chosen whenever possible.

Donor characteristics and hematopoietic stem cell transplantation outcome: experience of a single center in Southern Brazil

ABSTRACT Background: Hematopoietic stem cell transplantation is a curative treatment for many patients with hematological disorders. Donor-recipient genetic disparity, especially involving the human leukocyte antigen system is a critical factor for transplant outcome. Objective: To evaluate retrospectively donor characteristics and correlations with the occurrence of acute and chronic graft-versus-host disease, disease-free survival and overall survival in a Brazilian population submitted to allogeneic hematopoietic stem cell transplantation between 1994 and 2012 in a single center. Results: Three hundred and forty-seven consecutive transplantations were included. Related transplants (81.2%) were significantly more common than unrelated transplants (18.7%); donor and recipient median ages were 34 (range: 1-61) and 33 (range: 3-65) years respectively with donor HLAs being matched for 333 (95.9%) patients. Donor gender, cytomegalovirus status and ABO incompatibility did not influence the five-year overall survival. In univariate analyses, overall survival was negatively influenced by the presence of acute graft-versus-host disease (33% vs. 47%, respectively; p-value = 0.04), unrelated transplant (41.5% vs. 50.9%, respectively; p-value = 0.045) and donors aged over 40 years (41% vs. 52%, respectively; p-value = 0.03). Older donors were associated with a higher rate of acute (52% vs. 65.8%; p-value = 0.03) and chronic graft-versus-host disease (60% vs. 43%, respectively; p-value = 0.015). In multivariate analyses, acute graft-versus-host disease [relative risk (RR): 1.8; 95% confidence interval (CI): 1.1-29; p-value = 0.008] and older donors (RR: 1.6; 95% CI 1.11-2.24; p-value = 0.013) were associated with higher transplant-related mortality. Conclusions: In transplant patients, to have a donor older than 40 years of age seems to significantly increase the incidence of acute and chronic graft-versus-host disease and transplant-related mortality with no impact on disease-free survival and overall survival. In spite of the rather small cohort of patients, these findings are similar to what is described in the literature suggesting that a younger donor should be chosen whenever possible.

Characterization of Patients with Chronic Myeloid Leukemia Unresponsive to Tyrosine Kinase Inhibitors Who Underwent Allogeneic Hematopoietic Stem Cell Transplantation.

Background: Tyrosine kinase inhibitors (TKIs) were the first drugs to use an intracellular signaling molecule as a therapeutic target. Unresponsiveness to TKIs limits therapeutic options, making allogeneic hematopoietic stem cell transplantation (HSCT) the only option leading to molecular remission. The aim of this study is to characterize CML patients unresponsive to first- and/or second-generation TKI therapy who underwent HSCT and to describe the main factors associated with treatment failure. Subjects and Methods: Twenty one CML patients who underwent allogeneic HSCT and had previously used first- and/or second-generation TKIs from January 2005 to May 2014. Results: Of the 21 patients, 52.4% were male, with a median age of 49 years (23-65 years) and 85.7% had chronic phase CML at the time of diagnosis; 28.6% showed inadequate treatment adherence to TKI therapy. Thirteen patients were resistant and eight were intolerant to TKIs; additionally, nine did not have T315I mutation. Ten transplantations involved related donors, and more than a half of patients (11) died, three of which due to graft failure. Most patients who survived transplantation were in the chronic phase of disease at the time of HSCT. Conclusion: The population was composed mainly of young age patients at diagnosis, male, white, and coming from areas in the state of Rio Grande do Sul other than Porto Alegre and metropolitan region. Low adherence to TKI therapy may be related to unresponsiveness to treatment, especially in patients with acquired resistance, or this low adherence, together with the presence of molecular changes, may have led to the need for HSCT.

Immunosuppressive serum levels in allogeneic hematopoietic stem cell transplantation: pharmaceutical care contribution.

BACKGROUND: Cyclosporine and tacrolimus are limited by a narrow therapeutic window. Maintaining immunosuppressive drugs at desired levels may be difficult. Pharmaceutical care emerges as a philosophy of practice that enhances medication use and leads to a better control of serum concentration. OBJECTIVE: This study aims to evaluate the impact of pharmaceutical care in the maintaining of proper serum levels of immunosuppressive medications in patients who have undergone allo-HSCT. METHODS: The study had a quasi-experimental design that included a comparison group. The service model used was pharmacotherapy follow-up, according to an adaptation of the Dader method. The pharmacist consultation was carried out at a day-hospital or at the outpatient hematology clinic as needed. The intervention group consisted of 22 patients seen by a clinical pharmacist. The control group consisted of 44 patients that received standard care. This study aims to evaluate the impact of pharmaceutical care on keeping patient serum levels of cyclosporine and tacrolimus within the desired range. RESULTS: Control group displayed 65% of the proper serum levels of immunosuppressive agents. While In intervention group, the figure was 82% (p = 0.004). CONCLUSION: The role of the pharmacist in the multidisciplinary team may contribute to a greater success in attaining the patients' therapeutic targets with regard to the use of immunosuppressant.

Immunosuppressive serum levels in allogeneic hematopoietic stem cell transplantation: pharmaceutical care contribution

Background: Cyclosporine and tacrolimus are limited by a narrow therapeutic window. Maintaining immunosuppressive drugs at desired levels may be difficult. Pharmaceutical care emerges as a philosophy of practice that enhances medication use and leads to a better control of serum concentration. Objective: This study aims to evaluate the impact of pharmaceutical care in the maintaining of proper serum levels of immunosuppressive medications in patients who have undergone allo-HSCT. Methods: The study had a quasi-experimental design that included a comparison group. The service model used was pharmacotherapy follow-up, according to an adaptation of the Dader method. The pharmacist consultation was carried out at a day-hospital or at the outpatient hematology clinic as needed. The intervention group consisted of 22 patients seen by a clinical pharmacist. The control group consisted of 44 patients that received standard care. This study aims to evaluate the impact of pharmaceutical care on keeping patient serum levels of cyclosporine and tacrolimus within the desired range. Results: Control group displayed 65% of the proper serum levels of immunosuppressive agents. While In intervention group, the figure was 82% (p = 0.004). Conclusion: The role of the pharmacist in the multidisciplinary team may contribute to a greater success in attaining the patients’ therapeutic targets with regard to the use of immunosuppressant (AU)

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Fibrobroncoscopia no diagnóstico e decisão terapêutica de infecções respiratórias em pacientes neutropênicos febris hematológicos / Fiberoptic bronchoscopy in the diagnosis and therapeutic decision for respiratory infections in hematological febrile neutropenic patients

INTRODUÇÃO: A neutropenia febril é uma complicação frequente dos pacientes submetidos ao tratamento quimioterápico ou Transplante de Célula Tronco Hematopoiética (TCTH). A fibrobroncoscopia (FBC) flexível tem sido utilizada para auxiliar no diagnóstico de doenças pulmonares. No entanto, não há consenso em relação ao benefício do exame para estabelecer diagnóstico e alterar o tratamento das doenças pulmonares nesse contexto. Estudos prévios, retrospectivos e bastante heterogêneos, com pacientes imunocomprometidos não-HIV mostraram que o rendimento da fibrobroncoscopia para estabelecer diagnóstico etiológico varia de 13 a 81% e gera alteração de terapêutica em 5 e 51%. O objetivo deste estudo foi avaliar o rendimento da Fibrobroncoscopia, o risco ao procedimento em pacientes hematológicos e neutropênicos. MÉTODOS: Estudo transversal retrospectivo que avaliou pacientes com neoplasia hematológica e neutropenia febril e que tenham sido submetidos à fibrobroncoscopia diagnóstica entre janeiro de 2011 e dezembro de 2012 internados no Hospital de Clínicas de Porto Alegre. RESULTADOS: Foram incluídos 45 pacientes: 18 (36%) tiveram resultado positivo no Lavado Broncoalveolar (LAB), sendo que houve mudança na conduta terapêutica em 95% dos pacientes que apresentaram positividade no LAB. Com relação ao risco do procedimento tivemos uma taxa de 2,2% de complicação, com um paciente que apresentou dessaturação imediatamente após o procedimento. CONCLUSÃO: Apesar do número limitado de pacientes, nossos achados indicam que a realização da fibrobroncoscopia com LAB em pacientes neutropênicos é segura e com um rendimento semelhante aos descritos na literatura

INTRODUCTION: Febrile neutropenia is a common complication in patients undergoing chemotherapy or hematopoietic Stem Cell Transplantation (HSCT). Flexible fiberoptic bronchoscopy has been used to aid in the diagnosis of pulmonary diseases. However, there is no consensus regarding the benefit of the exam in establishing diagnosis and in changing the treatment of lung disease in this context. Previous retrospective studies, quite heterogeneous and with non-HIV immunocompromised patients, showed that the yield of fiberoptic bronchoscopy in establishing etiology ranges from 13% to 81%, and in changing therapy, from 5% to 51%. To evaluate the efficiency of Fiberoptic bronchoscopy and the procedure-related risk for neutropenic patients with hematologic malignancy. METHODS: This retrospective cross-sectional study analyzed the medical records of patients with hematologic malignancy with febrile neutropenia who had undergone diagnostic fiberoptic bronchoscopy between January 2011 and December 2012 at the Hospital de Clínicas de Porto Alegre. RESULTS: A total of 45 patients were included: 18 (36%) tested positive for bronchoalveolar lavage, with change in therapeutic management occurring for 95% of them. The procedure-related risk was 2.2%, with one patient showing desaturation immediately after the procedure. CONCLUSION: Despite the limited number of patients, our findings indicate that fiberoptic bronchoscopy in neutropenic patients is safe, and the results are similar to those previously reported

High prevalence of anemia in children and adult women in an urban population in southern Brazil.

This population-based study was designed to detect the prevalence of anemia in a healthy population of children (18 months to 7 years) and women (14 to 30 years) tested in 2006-2007 in the state of Rio Grande do Sul, Brazil as part of an effort to tackle this massive problem that still affects so many people in the XXI century. Anemia was defined according to the WHO. Capillary blood was measured and socioeconomic status was determined according to the Brazilian Association of Market Research Agencies. The median prevalence of anemia in 2198 children was 45.4% and in 1999 women 36.4%. Anemia decreased with age during childhood; although significantly more prevalent in lower classes individuals, it was also high in the upper classes. There are indirect evidences that the lack of iron supplementation and/or iron fortified food may play a role in it. Professionals and society wise measures of education have to be implemented in order to address possible biologic factors involved in childhood psychosocial development in southern Brazil.

Thrombosis after kidney transplantation.

The diagnosis of deep vein thrombosis (DVT) is unusual in patients with sickle cell disease (SCD). Despite the incidence of cerebral thrombosis in SCD patients due to vasooclusion, thrombotic manifestations in peripheral vessels are rare. Patients with homozygous SCD present a variety of renal abnormalities as a result of sickle crisis. In this group of patients, kidney transplantation has been performed in the renal endstage patients; with graft survival rates similar to that of the general transplant population at 1 year. However, patients with SCD experience an augmentation in the frequency of painful crises in the first year after transplantation, which has been attributed to concurrent elevations in hematocrit and plasma viscosity. Despite etiology, renal transplant patients are at increased risk for the development of thromboembolic events such as deep vein thrombosis and renovascular thrombosis after allograft procedure. These events can be due to a prothrombotic state generated by the use of immunosuppressive agents. Although other factors such as acquired or inherited disorders of the clotting system may increase the risk of thrombosis. Here, we report a case of a renal transplant patient with sickle cell disease who presented recurrent episodes of DVT and increase painful sickle episodes after kidney transplantation.

Características clínicas dos portadores de hemoglobinopatia S / Clinical characteristical of the hemoglobinopathy S patients

Os pacientes portadores de hemoglobinopatia S sofrem de uma anemia hemolítica crônica com repercussões sistêmicas. Estudo transversal retrospectivo com 64 pacientes portadores de hemoglobinopatia S, cujo objetivo foi descrever as suas manifestações clínicas. Com relação à gravidade clínica, 75,7 por cento dos portadores de anemia falciforme (SS) apresentaram doença grave, enquanto que 67,7 por cento dos portadores de traço falciforme (AS) apresentaram doença benigna, de acordo com os critérios de gravidade da doença. As alterações clínicas sistêmicas dos indivíduos portadores de hemoglobinopatia S estão presentes em algum momento de suas evoluções, sendo que o tipo e gravidade destas estão diretamente ligadas às variantes genéticas da doença