Cytokine profile of patients with chronic immune thrombocytopenia affects platelet count recovery after Helicobacter pylori eradication.

Helicobacter pylori eradication induces platelet recovery in a subgroup of patients with chronic immune thrombocytopenia (cITP), but the mechanisms involved are still not understood. We aimed to evaluate the effect of H. pylori eradication on platelet response and to identify the associated serum cytokine profile in 95 patients with cITP. Serum cytokine concentrations were determined by enzyme-linked immunosorbent assay prior to and 6 months after H. pylori eradication. Remission of cITP was observed in 17 (28·8%) of 59 patients in whom the bacterium was eradicated. Six months after treatment, a significant reduction in the concentrations of T-helper (Th) 1 and Th17 cells and an increase in T regulatory (Treg) and Th2-cell commitment cytokines were observed in patients who recovered, but not in those whose platelet count did not recover. Patients who had a platelet response to eradication of the bacteria had higher pre-treatment serum levels of γ-interferon (IFNG, IFN-γ), transforming growth factor-ß (TGFB1, TGF-ß) and interleukin 17 (IL17A, IL-17) than patients who did not respond, but only higher pre-treatment TGFB1 levels was independently associated with platelet response. In conclusion, amelioration of cITP after eradication of H. pylori was linked to a more efficient suppression of Th1 and Th17 response and a more pronounced Treg cell response.

The duration of the use of imatinib mesylate is only weakly related to elevated BNP levels in chronic myeloid leukaemia patients.

Cardiotoxicity has been feared as a potential side effect of imatinib therapy. Studies with short-term follow-up failed to identify an excess of cardiac events, but longer-term observations are needed to more definitely exclude this adverse effect. This study was designed to assess the cardiac effects of imatinib in patients under long-term treatment. We included 90 chronic myeloid leukaemia (CML) patients under imatinib therapy for a median treatment time of 3.3 years (mean age 48.9 ± 15.1 years). Patients underwent clinical evaluation, electrocardiography, echocardiography (two-dimensional, colour flow, tissue Doppler and strain imaging), brain natiuretic peptide (BNP) and troponin I measurements. Twenty healthy volunteers were included as a control group for strain measurements. The mean ejection fraction was 68 ± 7% and the median BNP level was 9.6 pg/ml (interquartile range [IQR] 5.7-17.0 pg/ml). Two patients had either an elevated BNP or a depressed ejection fraction (2.2%; 90%CI 0.9-6.8%). Most of troponin I measurements were lower than the detection limit, except for two patients. Longitudinal strain was similar to measurements in healthy controls. A weak relation was observed between log BNP and imatinib treatment duration and dose. There was no relation between these variables and left ventricle ejection fraction. In conclusion, matinib-related cardiotoxicity is an uncommon event in CML patients, even during long-term treatment. Therefore, its use should not be cause of great concern, and the usefulness of regular cardiac monitoring all patients while on imatinib therapy is questionable.

The use of imatinib mesylate has no adverse effects on the heart function. Results of a pilot study in patients with chronic myeloid leukemia.

To investigate cardiac effects of imatinib at an extended follow-up (median 12.4 months), 12 chronic myeloid leukemia patients underwent cardiac screening. No significant changes on the frequency of cardiovascular signs and symptoms, electrocardiographic abnormalities, echocardiographic measurements and BNP levels were observed. Median ejection fraction was 67% at baseline versus 68% at follow-up (median intra-patient change 0.5%). Median BNP levels were 8.3 versus 7.3pg/mL (median intra-patient change 0.2pg/mL). Troponin I measures were below the lower limit of detection, whereas strain measures were similar to healthy control. This pilot study suggests that it is probably safe to perform cardiac monitoring on an annual basis.

Transplante alogênico de células-tronco hematopoéticas em leucemias agudas: a experiência de dez anos do Hospital das Clínicas da UFMG / Allogeneic hematopoietic stem cells transplantation in acute leukemia: ten years of experience in the Hospital das Clínicas

As leucemias agudas são doenças com alta morbimortalidade para as quais o transplante alogênico de medula óssea é uma opção terapêutica eficaz. Neste artigo, relatamos a experiência de um centro brasileiro com pacientes apresentando leucemia aguda que receberam um enxerto de medula óssea ou células-tronco periféricas de um doador familiar HLA idêntico no período de julho de 1995 a dezembro de 2005. Foi realizado um estudo de coorte retrospectivo, analisando dados de 125 pacientes com mediana de idade de 28,7 anos. Oitenta e um pacientes (64,8 por cento) apresentavam leucemia mieloide aguda; 38 (30,4 por cento), leucemia linfoide aguda; e seis (4,8 por cento), leucemia bifenotípica. Trinta e dois pacientes encontravam-se em primeira remissão completa, 23 em segunda remissão e 70 com doença avançada (refratários, recidivados ou além da segunda remissão). A sobrevida global estimada em 10 anos foi de 22,9 por cento. Em relação à situação clínica do paciente no momento do transplante, a sobrevida global em dez anos foi de 56,3 por cento para pacientes em primeira remissão, 38 por cento para os pacientes em segunda remissão, e 3,7 por cento para os pacientes com doença avançada. Considerando-se os pacientes transplantados em primeira e segunda remissão, a evolução foi semelhante aos dados disponíveis na literatura. Entretanto, os resultados dos pacientes transplantados em fase avançada foram ruins, devendo-se discutir o papel do transplante para este grupo.

Acute leukemias are a group of diseases with high morbimortality. Allogeneic bone marrow transplantation is an efficacious therapeutic option for their treatment. We report the experience of a Brazilian center in respect to acute leukemia patients who received a bone marrow or peripheral blood allograft from a HLA-matched sibling from July 1995 to December 2005. Data were retrospectively collected. The median age of the 125 patients included in the study was 28.7 years. Eighty-one patients presented with acute myeloid leukemia, 38 with acute lymphocytic leukemia and six patients with biphenotypic leukemia. Thirty-two patients were in first complete remission, while 23 were in second remission and 70 were transplanted in an advanced disease stage (refractory, relapsed, or beyond second remission). Overall expected survival at 10 years was 22.9 percent; the expected survival was 56.3 percent, 38 percent, and 3.7 percent for patients in first remission, second remission and for patients with advanced disease, respectively. In conclusion, the evolution of patients transplanted in first or second remission was similar to other published studies. On the contrary, patients with advanced disease showed a dismal prognosis. The role of allogeneic transplantation in this group of patients should be further discussed.

Mieloma múltiplo: características clínicas e laboratoriais ao diagnóstico e estudo prognóstico / Multiple myeloma: clinical and laboratory characteristics in the diagnosis and prognostic study

O mieloma múltiplo (MM) caracteriza-se por expansão clonal plasmocitária na medula óssea e produção de imunoglobulina monoclonal, promovendo progressivamente destruição óssea, falência renal, supressão da hematopoiética e infecções. A identificação de fatores clínicos e laboratoriais ao diagnóstico é importante para predizer sobrevida. O sistema de estadiamento de Durie e Salmon (1975) é o mais utilizado e baseia-se na correlação entre parâmetros clínico-laboratoriais à massa tumoral. A combinação de β2 microglobulina e albumina sérica resultou em um sistema de estadiamento simples e confiável, conhecido como Sistema Internacional de Estadiamento (ISS), que tem sido reconhecido atualmente. O objetivo deste trabalho foi analisar as características clínicas e laboratoriais, ao diagnóstico, de pacientes portadores de MM e estudo de sobrevida. Realizou-se estudo de coorte não concorrente de 101 pacientes portadores de MM atendidos no Serviço de Hematologia do Hospital das Clínicas da UFMG, que receberam diagnóstico no período de abril de 1994 a 31 de outubro de 2006, através da coleta de dados contidos em prontuários médicos. Os pacientes foram acompanhados até maio de 2007. Foi feita análise descritiva das características ao diagnóstico e estudo de sobrevida, utilizando-se análise univariada pela técnica do produto-limite de Kaplan & Meier e teste de Log-Rank para comparação das curvas; já na análise multivariada, utilizou-se regressão múltipla de Cox. A mediana de idade dos pacientes foi de 63 anos de idade, 47,5 por cento eram homens e 52,5 por cento mulheres, sendo 50,6 por cento brancos, 33,3 por cento negros e 16,1 por cento pardos. Manifestações clínicas mais comuns foram: dor óssea (83,2 por cento), fraqueza (70,3 por cento) e perda de peso (40,6 por cento). Radiografia de esqueleto mostrou alterações em 83,8 por cento dos casos. Em relação ao sistema de estadiamento proposto por Durie & Salmon, 63 (62,4 por cento) pacientes...

Multiple myeloma (MM) is characterized by plasmocyte expansion in the bone marrow and the production of monoclonal immunoglobulin, causing bone destruction, renal failure, hematopoietic suppression and infections. Identification of clinical and laboratory factors in the diagnosis are important to predict survival. The Dürie/Salmon staging system, used for the disease, is based on the correlation of clinical and laboratory parameters on tumoral mass. Studies of the combination of β2 microglobulin and albumin resulted in a simple staging system, known as the International Staging System (ISS), which is currently being used. The objectives of this work were to analyze clinical and laboratory characteristics in the diagnosis of MM patients and a study of survival. A non-competitive cohort study was performed of 101 MM patients attended in the Hematology Service/Hospital das Clínicas-UFMG who were diagnosed in the period of April 1994 to October 2006.A descriptive analysis of the characteristics at diagnosis and a study of survival were made. The descriptive analysis was achieved using the Kaplan-Meier technique and the Log-Rank test utilized for a comparison of survival curves. The Cox regression test was used for multivariate analysis. The average age of the patients was 63 years, 47.5 percent were men and 52.5 percent women, with 50.6 percent being white, 33.3 percent black and 16.1 percent mulattos. The most common clinical manifestations were: bone pain (83.2 percent) and weakness (70.3 percent). Radiographies of the skeleton showed alterations in 83.8 percent of the cases. In respect to the Dürie/Salmon staging system, 63 (62.4 percent) patients were in stage III, 32 (31.7 percent) in stage II and 6 (5.9 percent) in stage I. Using the ISS classification, 22 (30.1 percent) patients were in stage III, 31 (42.5 percent) in stage II and 20 (27.4 percent) in stage I. Overall survival was 66.52 months with a follow-up of 20 months. In...

Mieloma múltiplo: verificação do conhecimento da doença em médicos que atuam na atenção primária à saúde / Multiple myeloma: assessment of knowledge of doctors working in primary healthcare

podem não ser identificados associados, dificultando e retardando o diagnóstico. A Atenção Primária à Saúde (APS) é a porta de entrada à rede de assistência à saúde no Brasil, por isso é importante o médico desse serviço reconhecer as características clínicas e laboratoriais do MM para conduzir adequadamente o paciente. Nosso objetivo foi verificar o conhecimento clínico e laboratorial sobre MM em médicos da APS. Foi realizado inquérito epidemiológico utilizando-se teste de múltipla escolha, aplicado em médicos das 137 Unidades Básicas de Saúde de Belo Horizonte (MG), entre outubro e dezembro de 2006. Doenças crônicas e neoplásicas em idosos foram reconhecidas como causas de anemia normocrômica e normocítica por 127 (94,1%) médicos;lesões osteolíticas ao Raio-X não foram associadas ao MM por 83 (61,5%); quadro clínico de hipercalcemia não foi clinicamente suspeitado pela maioria, 82 (60,7%); a eletroforese de proteínas foi incorretamente interpretada por 96 (71,1%) médicos eapenas 49 (36,3%) pensaram em MM diante de caso clínico característico. O tempo de graduação e de trabalho do médico na APS, assim como a existência de especialização médica, não influenciaram os resultados. Os sinais, sintomas e achados laboratoriais do MM não foram identificados por grande parte da população estudada, sendo umindicador da necessidade de maior interação entre os níveis de atenção secundária e primária, o que proporcionará educação compartilhada e continuada entre os profissionais dos diferentes níveis de atenção à saúde e maior eficiência no cuidado do paciente.

Multiple myeloma (MM) presents clinically with unspecific symptomswith an association that may not be identified, thus delaying the difficult diagnosis. Primary healthcare (PHC) is the doorway to the health system in Brazil; hence, doctors in this service should be able to recognize clinical and laboratorial characteristics of MM, inorder to manage the patient properly. Our objective was to verify clinical and laboratorial knowledge on MM of doctors working in PHC. An epidemiological survey was performed using a multiplechoice test completed by doctors of the 137 PHC units in Belo Horizonte(MG), between October and December 2006. Chronic and neoplastic diseases were recognized as causes of normochromic and normocytic anemia by 127 (94.1%) doctors; osteolytic lesions in the X-ray were not associated to MM by 83 (61.5%); clinical manifestations of hypercalcemia were not a clinical suspicion for the majority (82 - 60.7%); protein electrophoresis was incorrectly interpreted by 96 (71.1%) doctors and only 49 (36.3%) considered MM when presented with a characteristic clinical case. Neither timesince graduation, nor time working in PHCs, nor medical specialty influenced the results. A large proportion of the studied population failed to identify the signs, symptoms and laboratorial findings of MM, which indicates the need for a greater interaction between secondary and primary healthcare professionals, which will, in turn, promote shared and continuous education among professionals at the different levels of healthcare and a higher efficiency in patient care.

An evaluation of the cardiotoxicity of imatinib mesylate.

We studied 103 consecutive patients with chronic myeloid leukaemia on treatment with imatinib (IM) and 57 patients with chronic myeloproliferative disorders not treated with IM in order to evaluate its cardiotoxicity. There was no statistical difference regarding cardiac symptoms and signs, BNP levels and echocardiographic measurements for IM and control groups, except for peripheral oedema, more frequent in the IM group. Four patients in the IM group presented a BNP level >100pg/ml, one of them with depressed LVEF. IM was not related to systematic deterioration of cardiac function, but there is still a possibility of isolated cases of cardiotoxicity.

Leucemia mielóide aguda do adulto: análise retrospectiva de 99 casos / Acute myeloid leukemia in adult: retrospective analysis of 99 cases

Foram estudados retrospectivamente 99 pacientes adultos portadores de leucemia mielóide aguda diagnosticados e tratados no Hospital das Clínicas - Universidade Federal de Minas Gerais. Foram analisadas taxa de remissäo completa, sobrevida global e sobrevida em remissäo completa. Näo foram excluídos pacientes que tenham recebido apenas tratamentos suportivo, nem pacientes com leucemia secundária à mielodisplasia, ou secundária à quimioterapia. A idade do grupo foi 38 anos. A associaçäo de citosina arabinosídeo e daunoblastina ou mitoxantrone (7+3) foi utilizada em 78 casos na induçäo da remissäo. A terapia pós-remissäo consistiu de altas doses de Citosina arabinosídeo em 19 pacientes e manutençäo em 22. O tempo mínimo de seguimento em Remissäo Completa foi de 12 meses. A taxa de Remissäo Completa foi de 41,4 por cento. A Sobrevida Global estimada aos 3 anos Ú de 11 por cento + 4,0 por cento. A idade abaixo de 40 anos foi o fator mais favorável para a Sobrevida Global e Remissäo Completa (p = 0,023 e p= 0,0009, respectivamente). A Sobrevida em Remissäo Completa estimada aos 3 anos foi de 18,5 por cento + 7,0 por cento. A alta taxa de morte na induçäo foi o principal fator negativo, para remissäo completa e sobrevida global. O uso de Altas doses de Citosina Arabinosídeo foi o principal fator favorável para a sobrevida em remissäo completa (p=0,022). Para os pacientes que usaram Altas doses de Citosina Arabinosídeo, a sobrevida em Remissäo Completa estimada aos 24 meses foi de 32,5 por cento + 11,4 por cento.