Analysis of the interventions in antineoplastic therapy by a clinical pharmacy service at a tertiary hospital in Brazil.

BACKGROUND: Medication errors are avoidable occurrences that can assume clinically significant dimensions and impose relevant costs to the health system, especially in the context of antineoplastic therapy. OBJECTIVE: Assess the clinical significance and economic impacts of a clinical pharmaceutical service. This retrospective study consists of an analysis of pharmacy interventions and drug-related problems found in a review of electronic prescriptions referring to antineoplastic therapy of a public teaching tertiary hospital in Brazil. METHOD: Retrospective descriptive study obtained from electronic records of drug-related problems and pharmaceutical interventions related to antineoplastic therapy for oncological and hematological diseases, obtained through the pharmacotherapy review service. The accepted interventions were analyzed for the financial impact generated, evaluating your direct costs. The perception of clinical significance of a random sample of interventions was ascertained by the experts' opinion, using the Delphi method. RESULTS: The most frequent problem was a "lack of information to professionals" (25.06%), "problems as to the frequency and interval of doses" (22.90%), and "medication underdosing" (16.20%). Dose adjustment (31.50%) and clarifications (30.90%) were the most frequent pharmaceutical interventions. In the second round of Delphi, experts rated 77.77% of interventions as extremely significant and very significant. The main drugs reported in the interventions were cyclophosphamide, carboplatin, methotrexate, folinic acid, and monoclonal antibodies. The savings amounted to US$1,193,970.18 and involved mainly bortezomib, dactinomycin, and monoclonal antibodies. CONCLUSION: Clinical pharmacy services contributed to the rational use of medicines presenting clinical significance and avoiding waste of financial resources.

Oral Antineoplastics: Treatment Adherence and Medication Beliefs / Antineoplásicos Orais: Adesão ao Tratamento e Crenças sobre os Medicamentos / Agentes Antineoplásicos Orales: Adherencia al Tratamiento y Creencias sobre los Medicamentos

Introduction: Adherence to oral antineoplastics (OA) is an important indicator of therapeutic response related to personal, social, and structural factors. Objective: To determine rates of adherence to OA, investigating possible risk factors for nonadherence and to assess patient beliefs about medication, identifying opportunities for pharmaceutical intervention. Method: An analytical study was conducted with cancer patients using OA in 2015. Adherence to Refills and Medication Scale (ARMS) and Beliefs about Medicines Questionnaire (BMQ) were applied to assess adherence and beliefs about medication and treatment. Mann-Whitney, Chi-square, and Fisher's Exact tests were used for data analysis. Results: A total of 222 patients were interviewed, with a 92.8% adherence rate according to ARMS and 84.7% according to BMQ, in which the necessity-beliefs exceeded the concerns with the treatment and use of OA. Family income, treatment interruption, number and causes of interruptions, depression, and medication possession ratio were the risk factors identified. Comparison of BMQ domains showed that, in the adherent group, patient beliefs in the necessity of the medication exceeded their concerns about it. Conclusion: Understanding the patient's beliefs is a decisive factor in comprehending the risks related to nonadherence as well as in defining strategies to deal with it.

Introdução: A adesão aos antineoplásicos orais (AO) é um importante indicador de resposta terapêutica relacionada a fatores pessoais, sociais e estruturais. Objetivo: Determinar as taxas de adesão aos AO, investigando possíveis fatores de risco para a não adesão, e avaliar as crenças dos pacientes sobre medicamentos, identificando oportunidades de intervenção farmacêutica. Método: Estudo analítico realizado com pacientes com câncer em uso de AO em 2015. Escala de Adesão e Recarga dos Medicamentos (ARMS) e Questionário de Crenças sobre Medicamentos (BMQ) foram aplicados para avaliar a adesão e crenças sobre medicamentos e tratamento. Os testes de Mann-Whitney, qui-quadrado e exato de Fisher foram usados para análise de dados. Resultados: Foram entrevistados 222 pacientes, com taxa de adesão de 92,8%, segundo o ARMS e 84,7%, segundo o BMQ, no qual as crenças de necessidade excederam as preocupações com o tratamento e o uso de AO. Renda familiar, interrupção do tratamento, número e causas das interrupções, depressão e razão de posse de medicamentos foram os fatores de risco identificados. A comparação dos domínios do BMQ demostrou que, no grupo aderente, as crenças dos pacientes sobre a necessidade do medicamento excederam suas preocupações quanto a isso. Conclusão: Considerar as crenças do paciente é um fator decisivo para compreender os riscos relacionados à não adesão, bem como para definir estratégias para lidar com ela.

Introducción: La adherencia a antineoplásicos orales (AO) es un indicador importante de la respuesta terapéutica relacionada con factores personales, sociales y estructurales. Objetivo: Determinar tasas de adherencia a AO, investigar posibles factores de riesgo de incumplimiento y evaluar creencias de los pacientes sobre la medicación, identificando oportunidades para intervención farmacéutica. Método: Estudio analítico con pacientes con cáncer que usaban AO en 2015. Se aplicó Adherencia a la Recogida y Administración de la Medicación (ARMS) y Cuestionario de Creencias sobre Medicación (BMQ) para evaluar el cumplimiento y las creencias sobre medicación y tratamiento. Las pruebas de Mann-Whitney, Chi-cuadrado y Exacto de Fisher se utilizaron para análisis de datos. Resultados: Se entrevistó un total de 222 pacientes, con una tasa de adherencia de 92,8% según ARMS y 84,7% según BMQ, en la cual las creencias de necesidad excedieron preocupaciones con el tratamiento y uso de AO. Ingreso familiar, interrupción del tratamiento, número y causas de interrupciones, depresión y proporción de posesión de medicamentos fueron los factores de riesgo identificados. La comparación de los dominios de BMQ mostró que, en el grupo adherente, las creencias sobre necesidad de la medicación excedieron preocupaciones. Conclusión: La consideración de las creencias del paciente es un factor decisivo para comprender los riesgos relacionados con la no adherencia, así como para definir estrategias para afrontarla.

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

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...

Autologous Transplantation of Bone Marrow Adult Stem Cells for the Treatment of Idiopathic Dilated Cardiomyopathy / Transplante Autólogo de Células-Tronco Adultas para Tratamento da Cardiomiopatia Dilatada Idiopática

Background: Morbimortality in patients with dilated idiopathic cardiomyopathy is high, even under optimal medical treatment. Autologous infusion of bone marrow adult stem cells has shown promising preliminary results in these patients. Objective: Determine the effectiveness of autologous transplantation of bone marrow adult stem cells on systolic and diastolic left ventricular function, and on the degree of mitral regurgitation in patients with dilated idiopathic cardiomyopathy in functional classes NYHA II and III. Methods: We administered 4,54 x 108 ± 0,89 x 108 bone marrow adult stem cells into the coronary arteries of 24 patients with dilated idiopathic cardiomyopathy in functional classes NYHA II and III. Changes in functional class, systolic and diastolic left ventricular function and degree of mitral regurgitation were assessed after 3 months, 6 months and 1 year. Results: During follow-up, six patients (25%) improved functional class and eight (33.3%) kept stable. Left ventricular ejection fraction improved 8.9%, 9.7% e 13.6%, after 3, 6 and 12 months (p = 0.024; 0.017 and 0.018), respectively. There were no significant changes neither in diastolic left ventricular function nor in mitral regurgitation degree. A combined cardiac resynchronization and implantable cardioversion defibrillation was implanted in two patients (8.3%). Four patients (16.6%) had sudden death and four patients died due to terminal cardiac failure. Average survival of these eight patients was 2.6 years. Conclusion: Intracoronary infusion of bone marrow adult stem cells was associated with an improvement or stabilization of functional class and an improvement in left ventricular ejection fraction, suggesting the efficacy of this intervention. There were no significant changes neither in left ventricular diastolic function nor in the degree of mitral regurgitation. .

Fundamento: Pacientes portadores de cardiomiopatia dilatada idiopática apresentam alta morbimortalidade, mesmo em tratamento clínico otimizado. A infusão autóloga de células-tronco adultas da medula óssea mostrou resultados clínicos preliminares promissores nesses pacientes. Objetivo: Determinar a eficácia do transplante autólogo de células-tronco adultas da medula óssea sobre as funções sistólica e diastólica, e o grau de insuficiência mitral em pacientes portadores de cardiomiopatia dilatada idiopática em classes funcionais NYHA II e III. Métodos: Infundiram-se 4,54 x 108 ± 0,89 x 108 células-tronco adultas da medula óssea nas artérias coronárias de 24 pacientes com cardiomiopatia dilatada idiopática em classes funcionais NYHA II e III. Após 3 meses, 6 meses e 1 ano, avaliaram-se as mudanças de classe funcional, das funções ventricular esquerda sistólica e diastólica, e do grau da insuficiência mitral. Resultados: No seguimento, seis (25%) pacientes melhoraram sua classe funcional e oito (33,3%) mantiveram sua classe funcional inicial. A fração de ejeção ventricular esquerda aumentou 8,9%, 9,7% e 13,6%, após 3 e 6 meses e 1 ano (p = 0,024; p = 0,017 e p = 0,018), respectivamente. A função diastólica ventricular esquerda e o grau de insuficiência mitral não demonstraram mudanças significativas. Dois pacientes (8,3%) receberam cardioversor e ressincronizador implantável. Ocorreram quatro (16,6%) mortes súbitas e quatro (16,6%) mortes por insuficiência cardíaca terminal. A sobrevida média desses oitos pacientes foi de 2,6 anos. Conclusão: A infusão intracoronariana de células-tronco adultas da medula óssea em pacientes com cardiomiopatia dilatada idiopática promoveu melhora ...

Autologous transplantation of bone marrow adult stem cells for the treatment of idiopathic dilated cardiomyopathy.

BACKGROUND: Morbimortality in patients with dilated idiopathic cardiomyopathy is high, even under optimal medical treatment. Autologous infusion of bone marrow adult stem cells has shown promising preliminary results in these patients. OBJECTIVE: Determine the effectiveness of autologous transplantation of bone marrow adult stem cells on systolic and diastolic left ventricular function, and on the degree of mitral regurgitation in patients with dilated idiopathic cardiomyopathy in functional classes NYHA II and III. METHODS: We administered 4,54 x 10(8) ± 0,89 x 10(8) bone marrow adult stem cells into the coronary arteries of 24 patients with dilated idiopathic cardiomyopathy in functional classes NYHA II and III. Changes in functional class, systolic and diastolic left ventricular function and degree of mitral regurgitation were assessed after 3 months, 6 months and 1 year. RESULTS: During follow-up, six patients (25%) improved functional class and eight (33.3%) kept stable. Left ventricular ejection fraction improved 8.9%, 9.7% e 13.6%, after 3, 6 and 12 months (p = 0.024; 0.017 and 0.018), respectively. There were no significant changes neither in diastolic left ventricular function nor in mitral regurgitation degree. A combined cardiac resynchronization and implantable cardioversion defibrillation was implanted in two patients (8.3%). Four patients (16.6%) had sudden death and four patients died due to terminal cardiac failure. Average survival of these eight patients was 2.6 years. CONCLUSION: Intracoronary infusion of bone marrow adult stem cells was associated with an improvement or stabilization of functional class and an improvement in left ventricular ejection fraction, suggesting the efficacy of this intervention. There were no significant changes neither in left ventricular diastolic function nor in the degree of mitral regurgitation.

Tumor estromal gastrointestinal: experiência no tratamento da doença localizada e avançada no Hospital de Clínicas da Universidade Federal do Paraná / Gastrointestinal stromal tumor: experience in the treatment of localized and advanced disease at the Clinical Hospital of Parana Federal University

Introdução: Tumores estromais gastrointestinais (GIST) são neoplasias raras que se originam das células intersticiais de Cajal. Objetivo: Descrever a experiência do Hospital de Clínicas de Curitiba no tratamento do GIST localizado e avançado, com análise das características clínicas e anatomopatológicas e uso do imatinibe. Método: Estudo retrospectivo com 32 pacientes com diagnóstico por imuno-histoquímica, c-Kit positivo, no período de 2003 a 2008. Resultados: Idade mediana: 66 anos; tamanho mediano do tumor de 8,4 cm; e as localizações mais frequentes foram estômago em 46,9 por cento e intestino delgado em 40,9 por cento. Pacientes com alto risco de agressividade: 37,5 por cento; apresentavam doença localizada no diagnóstico 23 pacientes: 39,1 por cento recaíram e 9 com doença avançada. O seguimento mediano foi de 43,7 meses, com sobrevida global em 5 anos no grupo total de 56,2 por cento. Na doença localizada, a sobrevida global em 5 anos foi de 73,8 por cento e na avançada de 37,5 por cento (p=0,03). Não ocorreu impacto dos fatores prognósticos na sobrevida. Utilizou-se omesilato de imatinibe em 16 pacientes: 43,8 por cento por metástase inicial, 37,5 por cento recaída a distância, 12,5 por cento recaída local e 6,2 por cento margem comprometida. A sobrevida global com uso do imatinibe mediana foi de 53 meses e a sobrevida livre de primeira progressão de 32,9 meses. Houve boa tolerabilidade ao imatinibe e apenas dois pacientes utilizaram osunitinibe. Conclusão: A maioria dos tumores era grande, de localização gástrica e de alto risco de agressividade. A taxa de recaída na doença localizada foi alta. E a sobrevida global dos pacientes de doença localizada e que utilizaram o imatinibe foi considerada satisfatória.

Early lymphocyte recovery as a predictor of outcome, including relapse, after hematopoietic stem cell transplantation.

BACKGROUND: Despite advances in the treatment of acute leukemia, many patients need to undergo hematopoietic stem cell transplantation. Recent studies show that early lymphocyte recovery may be a predictor of relapse and survival in these patients. OBJECTIVE: To analyze the influence of lymphocyte recovery on Days +30 and +100 post-transplant on the occurrence of relapse and survival. METHODS: A descriptive, retrospective study was performed of 137 under 21-year-old patients who we resubmitted to hematopoietic stem cell transplantation for acute leukemia between 1995 and 2008. A lymphocyte count < 0.3 x 10(9)/L on Day +30 post-transplant was considered to be inadequate lymphocyte recovery and counts ≥ 0.3 x 10(9)/L were considered adequate. Lymphocyte recovery was also analyzed on Day +100 with < 0.75 x 10(9)/Land ≤ 0.75 x 10(9)/L being considered inadequate and adequate lymphocyte recovery, respectively. RESULTS: There was no significant difference in the occurrence of relapse between patients with inadequate and adequate lymphocyte recovery on Day +30 post-transplant. However, the transplant-related mortality was significantly higher in patients with inadequate recovery on Day +30. Patients with inadequate lymphocyte recovery on Day +30 had worse overall survival and relapse-free survival than patients with adequate recovery. There was no significant difference in the occurrence of infections and acute or chronic graft-versus-host disease. Patients with inadequate lymphocyte recovery on Day +100 had worse overall survival and relapse-free survival and a higher cumulative incidence of relapse. CONCLUSION: The evaluation of lymphocyte recovery on Day +30 is not a good predictor of relapse after transplant however patients with inadequate lymphocyte recovery had worse overall survival and relapse-free survival. Inadequate lymphocyte recovery on Day +100 is correlated with higher cumulative relapse as well as lower overall survival and relapse-free survival.

Early lymphocyte recovery as a predictor of outcome, including relapse, after hematopoieticstem cell transplantation

BACKGROUND: Despite advances in the treatment of acute leukemia, many patients need to undergo hematopoietic stem cell transplantation. Recent studies show that early lymphocyte recovery may be a predictor of relapse and survival in these patients. OBJECTIVE: To analyze the influence of lymphocyte recovery on Days +30 and +100 post-transplant on the occurrence of relapse and survival. METHODS: A descriptive, retrospective study was performed of 137 under 21-year-old patients who were submitted to hematopoietic stem cell transplantation for acute leukemia between 1995 and 2008. A lymphocyte count < 0.3 x 10(9)/L on Day +30 post-transplant was considered to be inadequate lymphocyte recovery and counts > 0.3 x 10(9)/L were considered adequate. Lymphocyte recovery was also analyzed on Day +100 with < 0.75 x 10(9)/Land < 0.75 x 10(9)/L being considered inadequate and adequate lymphocyte recovery, respectively. RESULTS: There was no significant difference in the occurrence of relapse between patients with inadequate and adequate lymphocyte recovery on Day +30 post-transplant. However, the transplant-related mortality was significantly higher in patients with inadequate recovery on Day +30. Patients with inadequate lymphocyte recovery on Day +30 had worse overall survival and relapse-free survival than patients with adequate recovery. There was no significant difference in the occurrence of infections and acute or chronic graft-versus-host disease. Patients with inadequate lymphocyte recovery on Day +100 had worse overall survival and relapse-free survival and a higher cumulative incidence of relapse. CONCLUSION: The evaluation of lymphocyte recovery on Day +30 is not a good predictor of relapse after transplant however patients with inadequate lymphocyte recovery had worse overall survival and relapse-free survival. Inadequate lymphocyte recovery on Day +100 is correlated with higher cumulative relapse as well as lower overall survival and relapse-free survival.

Transplante de células-tronco hematopoéticas em crianças e adolescentes com leucemia aguda: experiência de duas instituições brasileiras / Hematopoietic stem cell transplantation in children and adolescents with acute leukemia: experience of two Brazilian institutions

O transplante de células-tronco hematopoéticas (TCTH) é o tratamento de escolha para leucemias agudas de alto risco. Apesar da melhora na sobrevida destes pacientes, a recidiva continua sendo a maior causa de óbito pós-transplante de células-tronco hematopoéticas. O objetivo deste trabalho foi analisar os resultados dos transplantes realizados em crianças com leucemia aguda em duas instituições brasileiras. Realizou-se estudo retrospectivo de 208 pacientes transplantados entre 1990-2007. Mediana de idade: 9 anos; 119 pacientes com leucemia linfoide aguda (LLA) e 89 com leucemia mieloide aguda (LMA). Doença precoce: CR1 e CR2. ... 14/195 pacientes tiveram falha primária de pega (8 por cento). Não houve diferença na sobrevida global e sobrevida livre de recaída entre pacientes com leucemia linfoide aguda e leucemia mieloide aguda, entre transplantes aparentados e não aparentados, tampouco entre as fontes de células utilizadas. O desenvolvimento da doença do enxerto contra hospedeiro (DECH) aguda ou crônica também não influenciou a sobrevida global e sobrevida livre de recaída. Pacientes com leucemia linfoide aguda condicionados com irradiação corporal total (TBI) apresentaram melhor sobrevida global e sobrevida livre de recaída (p<0,001). Cento e dezoito pacientes morreram entre 1-1.654 dias pós-transplante de células-tronco hematopoéticas (M:160). Mortalidade relacionada a transplante (MRT) (dia+100): 16 por cento. Incidência cumulativa de recaída: 40 por cento (3 anos). Pacientes com doença avançada tiveram menor sobrevida global e sobrevida livre de recaída (três anos)(p<0,001). Na análise multivariada, o status da doença foi o principal fator associado ao aumento da sobrevida global e sobrevida livre de recaída. Nossos resultados mostram que é possível se atingir uma boa sobrevida para pacientes com doença precoce e também mostram a baixa eficácia naqueles com doença avançada.

Hematopoietic Stem Cell transplantation (HSCT) is the treatment of choice for patients with high-risk leukemia. In spite of this, relapse remains a major cause of death of these patients. Our objective was to analyze the outcomes of patients with acute leukemia submitted to hematopoietic stem cell transplantation in two Brazilian institutions... There were no differences in the overall survival and event free survival between patients with acute lymphocytic leukemia and acute myeloid leukemia, between sources of cells used or between those who developed acute or chronic graft-versus-host disease (GVHD). When comparing transplants from related and unrelated donors, there was no difference in the overall survival. Patients with acute lymphocytic leukemia receiving the total body irradiation (TBI) conditioning regimen had better overall survival and event free survival (p<0.001). One hundred and eighteen patients died between 0 and 1654 days after hematopoietic stem cell transplantation (M: 160 days). Transplantation-related-mortality (TRM) at D+100 was 16 percent and cumulative incidence of relapse was 40 percent (3 years). Patients with advanced disease had lower 3-year overall survival and event free survival (p<0.001). Multivariate analysis showed that disease status was the most significant factor associated with higher event free survival and overall survival . Our results show that children and adolescents transplanted with early disease can achieve considerable overall survival and also highlights the inefficacy of hematopoietic stem cell transplantation for patients with advanced disease.

Análise retrospectiva dos pacientes infectados por RSV na unidade de transplante de medula óssea / RSV infection after allogeneic hematopoietic stem cell transplanttrans planted in a single institutionation (HSCT): analysis of 59 patients

O vírus sincicial respiratório (RSV) é considerado uma causa importante de morbi-mortalidade em pacientes submetidos ao transplante de células-tronco hematopoéticas (TCTH). Mesmo com o uso da ribavirina inalatória (RI), as taxas de mortalidade são de 30 por cento a 40 por cento . O objetivo deste trabalho foi analisar o perfil dos pacientes infectados pelo RSV e a eficácia do tratamento com RI. Realizou-se uma análise retrospectiva de 59 pacientes submetidos ao TCTH com infecção confirmada pelo RSV (métodos de IFI ou PCR) entre 02/1991 e 02/2008. A RI foi administrada por 12 horas, na dose de 5 g diluída 200 ml de água destilada, por cinco dias. Quinze pacientes apresentaram infecções (TRI) do trato respiratório inferior e 44 pacientes apresentaram infecções (TRS) de vias aéreas superiores. No grupo tratado (n=50), quarenta apresentaram infecções no TRS versus dez TRI; no grupo não tratado, quatro TRS versus cinco TRI. Foram constatados vinte óbitos (33,8 por cento), sendo que 13 desses pacientes (65 por cento dos óbitos) tiveram suas mortes relacionadas ao RSV. Dentre estes, nove pacientes foram a óbito antes da instituição da RI como terapia padrão. A sobrevida global (SG) de todos os pacientes foi de 8,3 meses, sendo 66 por cento para o grupo que utilizou RI versus 11,1 por cento no grupo não tratado(p=0,001). No entanto, a SG foi inferior nos pacientes que apresentaram infecções no TRI (37,5 por cento) quando comparadas às infecções do TRS (65,1 por cento), p=0,007. No modelo de regressão de Cox, a única variável independente encontrada foi o tratamento com RI (p=0,001).

Respiratory syncytial virus (RSV) causes significant mortality in patients submitted to SCT. Despite the use of ribavirin aerosols (RA), mortality rates are still between 30 and 40 percent in many centers. The objective of this study was to analyze the clinical course and outcome of 59 patients who developed RSV infections after SCT in a single institution. In this retrospective analysis, the diagnosis of RSV infection was confirmed in 59 patients submitted to HSCT. RA was administrated during 12 hours at a dose of 5g diluted in 200 mL of distillated water, for 5 days. Fifteen patients presented with upper respiratory tract (URT) infection and 44 patients presented with lower respiratory tract (LRT) infection. In the group of patients who received RA (n=50), 40 had URT infections and 10 had LRT infections. In patients who did not receive RA, 3 had URT infections and 6 had LRT infections. Twenty patients died (33.8 percent) with the main cause of death of 13 patients being RSV infection (all these patients required mechanical ventilation). Nine patients died before RA therapy became standard treatment for RSV (before 1992). The overall survival of patients treated with RA was 66 percent. However, the overall survival was lower in patients who had LRT infections (37.5 percent) compared with those who had URT infections (67.5 percent - p=0.007). In the multivariate analysis, only the use of RA affected overall survival (p=0.001).

Anemia hemolítica microangiopática induzida por tacrolimus e ciclosporina A / Microangiopathic hemolytic anemia induced by tacrolimus and ciclosporine A

Relatamos caso raro de anemia hemolítica microangiopática em paciente após transplante hepático por cirrose Child B causada por deficiência de alfa1-antitripsina. Após análise clínica e laboratorial extensa, concluiu-se que o quadro de hemólise foi causado pela medicação imunossupressora utilizada após transplante. Inicialmente foi utilizado tacrolimus que, posteriormente, foi substituído por ciclosporina A, entretanto não houve melhora da hemólise. Após suspensão das duas drogas, houve melhora importante clínica do paciente, com normalização dos parâmetros hematológicos.

We report a rare case of acute hemolysis in a patient after liver transplant for Child B cirrhosis caused by alfa1-antitripsine deficiency. History and laboratorial examinations indicated that the most probable cause of the hemolysis was the use of the immunosupressor tacrolimus and later Cyclosporine A. After the discontinuation of these drugs, there was improvement in the clinical condition of the patient, with a compensated hemolytic anemia.

Neurological complications of hematopoietic stem cell transplantation (HSCT): a retrospective study in a HSCT center in Brazil.

We present the neurological complications evaluated in a series of 1000 patients who underwent hematopoietic stem cell transplantation (HSCT). Central nervous system (CNS) neurological complications, particularly brain hemorrhages, were the most common, followed by seizures and CNS infections. An unusual neurological complication was Wernicke's encephalopathy. Less frequent neurological complications were metabolic encephalopathy, neuroleptic malignant syndrome, reversible posterior leukoencephalopathy syndrome, brain infarct and movement disorders. The most common neurological complication of the peripheral nervous system was herpes zoster radiculopathy, while peripheral neuropathies, inflammatory myopathy and myotonia were very rarely found.

Neurological complications of hematopoietic stem cell transplantation (HSCT): a retrospective study in a HSCT center in Brazil / Complicações neurológicas do transplante de células tronco hematopoiéticas (TCTH): estudo retrospectivo em um centro de TCTH no Brasil

We present the neurological complications evaluated in a series of 1000 patients who underwent hematopoietic stem cell transplantation (HSCT). Central nervous system (CNS) neurological complications, particularly brain hemorrhages, were the most common, followed by seizures and CNS infections. An unusual neurological complication was Wernicke's encephalopathy. Less frequent neurological complications were metabolic encephalopathy, neuroleptic malignant syndrome, reversible posterior leukoencephalopathy syndrome, brain infarct and movement disorders. The most common neurological complication of the peripheral nervous system was herpes zoster radiculopathy, while peripheral neuropathies, inflammatory myopathy and myotonia were very rarely found.

Apresentamos as complicações neurológicas avaliadas em uma série de 1000 pacientes submetidos ao transplante de células tronco hematopoiéticas (TCTH). As complicações neurológicas do sistema nervoso central foram as mais encontradas, particularmente as hemorragias encefálicas, seguidas por crises convulsivas e por infecções. Uma complicação peculiar foi a encefalopatia de Wernicke. Menos freqüentemente foram encontrados casos de encefalopatia metabólica, síndrome maligna neuroléptica, leucoencefalopatia posterior reversível, infarto cerebral e os distúrbios do movimento. Entre as complicações neurológicas do sistema nervoso periférico a mais encontrada foi a radiculopatia pelo herpes zoster, enquanto que raramente se observaram casos de polineuropatias periféricas, miopatia inflamatória e de miotonia.

Allogeneic bone marrow transplantation for severe aplastic anemia patients with risk factors for poor prognosis: is fludarabine a requirement? / Transplante alogênico de medula óssea em portadores de anemia aplásica severa com fatores de mau prognóstico: é necessário fludarabina?

Hematopoietic progenitor cell transplantation from HLA-identical sibling donors cures 70-90 percent of Severe Aplastic Anemia (sAA) patients. Older age, heavy exposure to transfusions, immunosuppression treatment (IST) with a long interval from diagnosis to transplant and infection at procedure are associated with poor outcomes. We transplanted 18 patients with sAA and at least one risk factor (RF) for poor prognosis (age >35 years, >50 transfusions prior to transplant, unresponsiveness to previous IST and bacterial or fungal infection at transplant) from 2001 to 2005, using cyclophosphamide (CY - 5 patients) or busulfan plus CY (13 patients). Sixteen patients engrafted, two died with no engraftment, three patients had evidence of graft failure at days +67, +524 and +638 (two died and one was rescued with IST). Grade III/IV mucositis occurred in 39 percent but neither aGVHD nor cGVHD were observed. The Kaplan-Meier probability of survival was 75 percent at 2.14 years, with a trend favoring survival by number of RF (1 versus =2 RF) (P = 0.06). These results are comparable to recent data reported with fludarabine-based conditioning in patients with poor prognosis sAA. Due to the small sample size, prospective clinical trials with larger cohorts of patients are needed to confirm the real benefits of fludarabine-based conditioning, and also to define the best agent(s) to be associated with Fludarabine as preparative regimen for sAA patients with poor prognosis.

Transplante de medula óssea de doador irmão HLA-idêntico pode curar 70 por cento-90 por cento dos portadores de anemia aplásica severa (AAs). Pacientes mais idosos, muito transfundidos, longamente tratados com imunossupressão (IS) e com infecções ao tempo do transplante têm pior evolução. Nós transplantamos 18 pacientes com AAs e pelo menos um dos fatores associados a pior prognóstico (idade >35 anos, >50 transfusões antes do transplante, falta de resposta à imunossupressão prévia e infecção bacteriana ou fúngica ao transplante) de 2001 a 2005, com ciclofosfamida (Cy - 5 pacientes) ou bussulfan mais Cy (13 pacientes). Dezesseis pacientes apresentaram pega do enxerto, dois morreram sem pega, três tiveram rejeição aos dias +67, +524 e +638 (dois morreram e um foi resgatado com IS). Mucosite grau III/IV ocorreu em 39 por cento e não observamos DECH aguda ou crônica. A probabilidade de sobrevida pelo método de Kaplan-Meier foi de 75 por cento aos 2,14 anos, e uma tendência a melhor sobrevida foi encontrada entre os portadores de apenas um fator de risco ao transplante (P: .06). Estes resultados são comparáveis a recentes relatos de literatura envolvendo condicionamentos baseados em fludarabina para tratar pacientes com alto risco. Devido à pequena amostra analisada, estudos clínicos prospectivos com maior número de pacientes são necessários, visando comprovar o real benefício dos condicionamentos baseados em fludarabina, definir o melhor agente a ser a ela associado e assim obter o melhor condicionamento para portadores de AAs com fatores de mau prognóstico para o transplante.

[Prevalence of hemoglobin S in the State of Paraná, Brazil, based on neonatal screening]. / Prevalência da hemoglobina S no Estado do Paraná, Brasil, obtida pela triagem neonatal.

The Brazilian Ministry of Health created the National Neonatal Screening Program under ruling no. 822/2001, including neonatal screening for hemoglobinopathies. In the State of Paraná, neonatal screening is conducted by the Ecumenical Foundation for the Protection of the Handicapped. The prevalence rates were determined for homozygous and heterozygous hemoglobin S and Sbeta-thalassemia. Blood samples drawn on filter paper were examined by isoelectric focusing (IEF) and high-performance liquid chromatography (HPLC). From January 2002 to December 2004, 548,810 newborns were screened, with the detection of 21 with FS, two FSA/FS, and four FSA. After confirmatory tests at six months of age, 12 were defined as sickle-cell anemia, or a prevalence of 2.2:100,000 newborns; Sbeta-thalassemia was confirmed in 15 (2.7:100,000 newborns); and 8,321 newborns were diagnosed as heterozygous HbS (1,500:100,000 newborns). HbS prevalence in Paraná (in southern Brazil) is lower than in the Central-West, North, and Northeast of the country. Ethnic origin of the population, fetal deaths, and non-random procreation may contribute to the relatively low number of homozygous individuals in the State. Sbeta-thalassemia interaction suggests the presence of Euro-Mediterranean peoples in this population's miscegenation.

Prevalência da hemoglobina S no Estado do Paraná, Brasil, obtida pela triagem neonatal / Prevalence of hemoglobin S in the State of Paraná, Brazil, based on neonatal screening

O Ministério da Saúde instituiu o Programa Nacional de Triagem Neonatal através da Portaria nº. 822/GM, incluindo a pesquisa das hemoglobinopatias nos recém-nascidos. No Paraná, é realizada pela Fundação Ecumênica de Proteção ao Excepcional. Determinou-se a prevalência da hemoglobina S em homozigose, heterozigose e Sbeta-talassemia no estado. O sangue coletado em papel filtro foi examinado por focalização isoelétrica e cromatografia líquida de alta precisão (HPLC). De janeiro de 2002 a dezembro de 2004, foram triados 548.810 recém-nascidos e detectados 21 recém-nascidos com os resultados FS, dois FSA e/ou FS e quatro FSA. Após exames confirmatórios aos seis meses de idade, 12 foram definidos como anemia falciforme, com prevalência de 2,2:100 mil recém-nascidos; a interação Sbeta-talassemia foi confirmada em quinze (2,7:100 mil recém-nascidos); e 8.321 recém-nascidos foram diagnosticados como heterozigotos para HbS (1.500:100 mil recém-nascidos). A prevalência da HbS no Paraná é menor do que nas regiões Centro-Oeste, Norte e Nordeste do país. Origem étnica da população, óbitos fetais e casamentos preferenciais podem estar contribuindo para não haver maior número de homozigotos no estado. A interação Sbeta-talassemia sugere presença de povos euro-mediterrâneos na miscigenação dessa população.

The Brazilian Ministry of Health created the National Neonatal Screening Program under ruling no. 822/2001, including neonatal screening for hemoglobinopathies. In the State of Paraná, neonatal screening is conducted by the Ecumenical Foundation for the Protection of the Handicapped. The prevalence rates were determined for homozygous and heterozygous hemoglobin S and Sbeta-thalassemia. Blood samples drawn on filter paper were examined by isoelectric focusing (IEF) and high-performance liquid chromatography (HPLC). From January 2002 to December 2004, 548,810 newborns were screened, with the detection of 21 with FS, two FSA/FS, and four FSA. After confirmatory tests at six months of age, 12 were defined as sickle-cell anemia, or a prevalence of 2.2:100,000 newborns; Sbeta-thalassemia was confirmed in 15 (2.7:100,000 newborns); and 8,321 newborns were diagnosed as heterozygous HbS (1,500:100,000 newborns). HbS prevalence in Paraná (in southern Brazil) is lower than in the Central-West, North, and Northeast of the country. Ethnic origin of the population, fetal deaths, and non-random procreation may contribute to the relatively low number of homozygous individuals in the State. Sbeta-thalassemia interaction suggests the presence of Euro-Mediterranean peoples in this population's miscegenation.

Comparative study of abnormalities of central nervous system in children and adults autopsied after bone marrow transplantation / Estudo comparativo das alterações no sistema nervoso central de crianças e adultos autopsiados após transplante de medula óssea

BACKGROUND: We compare neuropathological abnormalities in children and adults after bone marrow transplantation (BMT) by means of autopsy in the Department of Medical Pathology, Universidade Federal do Paraná (UFPR), Brazil. METHODS: Autopsy reports of 180 patients were reviewed. They were divided in two groups: patients under 15 years old and those 15 or older. Age, gender, clinical diagnosis at time of BMT, survival time, neuropathological abnormalities and cause of death were analyzed. RESULTS: In children (26.6 percent of total) and in the adult group (73.4 percent of total), the main clinical diagnoses prior to BMT were, respectively, severe aplastic anemia (31.2 percent) and chronic myeloid leukemia (36.3 percent). The mean survival time for children was 102.6 days and for adults, 185.9 days after BMT. Brain lesions were considered cause of death in 20.8 percent of pediatric cases and 11.3 percent of the adult group. Neuropathological abnormalities were morphologically similar in children and adults, with the following respectively prevalence: cerebrovascular diseases in 58.3 and 56 percent (p = 0.8655), neurotoxoplasmosis in 6.2 percent and 3 percent (p = 0.3856) and infections in 27 and 25.7 percent (p = 0.8489). CONCLUSIONS: The pediatric patients had shorter survival than adults, with increasing prevalence of neurotoxoplasmosis, and brain lesions were considered cause of death in twice as many as compared to adult patients.

INTRODUÇÃO: Foram comparadas as anormalidades encontradas no sistema nervoso central de adultos e crianças submetidos à autópsia após transplante de medula óssea (TMO) no Departamento de Patologia Médica da Universidade Federal do Paraná (UFPR). MÉTODOS: Relatórios das autópsias de 180 pacientes foram revistos. Foram considerados crianças os pacientes abaixo de 15 anos; adultos, aqueles com 15 ou mais. A idade, o sexo, o diagnóstico clínico na época do TMO, o tempo de sobrevivência, as anormalidades neuropatológicas e a causa da morte foram analisados. RESULTADOS: Nas crianças (26,6 por cento do total) e nos adultos (73,4 por cento do total) o principal diagnóstico clínico prévio ao TMO foi, respectivamente, anemia aplásica severa (31,2 por cento) e leucemia mielóide crônica (36,3 por cento). O tempo médio de sobrevivência pós-TMO para crianças foi de 102,6 dias; para os adultos, 185,9. Lesões cerebrais foram consideradas causa de morte em 20,8 por cento dos casos pediátricos e 11,3 por cento do grupo adulto. As anormalidades neuropatológicas foram morfologicamente similares nas crianças e nos adultos e apresentaram, respectivamente, as seguintes prevalências: doenças cerebrovasculares em 58,3 por cento e 56 por cento (p = 0,8655), neurotoxoplasmose em 6,2 por cento e 3 por cento (p = 0,3856) e infecções em 27 e em 25,7 por cento (p = 0,8489). CONCLUSÕES: As crianças tiveram sobrevida menor, maior número de casos de neurotoxoplasmose e duas vezes mais lesões graves do sistema nervoso central que o grupo adulto.

HLA-matched related donor hematopoietic cell transplantation in 43 patients with Fanconi anemia conditioned with 60 mg/kg of cyclophosphamide.

Cells from Fanconi anemia (FA) patients are hypersensitive to alkylating agents and radiation traditionally used as conditioning regimens for marrow cell transplantation, and patients experience serious toxicities. To reduce toxicities, we used progressively lower doses of cyclophosphamide (CY) for conditioning. Here, we report the results in 43 FA patients who received marrow transplantation from HLA-matched related donors (37 siblings and 6 other relatives). Conditioning consisted of 15 mg CY/kg/day for 4 days along with Mesna. Methotrexate and cyclosporine were given for graft-versus-host disease (GVHD) prophylaxis. Forty patients (93%) are alive with a median follow-up of 3.7 (range 0.6 to 7.9) years. One patient with primary graft failure was successfully retransplanted. Three of 4 patients with late graft failures were retransplanted, and 2 of those are alive; 1 died before a second marrow graft. Twelve patients including 3 with rejection had cytogenetic abnormalities in their marrow cells before transplantation. Acute grade II-III and chronic GVHD (aGVHD, cGVHD) were seen in 17% and 28.5% of patients, respectively. These results confirm and extend our previous observations that conditioning with 60 mg CY/kg allows for sustained engraftment of HLA-matched related marrow grafts in most FA patients and is associated with low toxicity, low incidences of aGVHD and cGVHD, and excellent long-term survival.