Epstein-Barr virus: general factors, virus-related diseases and measurement of viral load after transplant

The Epstein-Barr virus is responsible for infectious mononucleosis syndrome and is also closely associated to several types of cancer. The main complication involving Epstein-Barr virus infection, both in recipients of hematopoietic stem cells and solid organs, is post-transplant lymphoproliferative disease. The importance of this disease has increased interest in the development of laboratory tools to improve post-transplant monitoring and to detect the disease before clinical evolution. Viral load analysis for Epstein-Barr virus through real-time polymerase chain reaction is, at present, the best tool to measure viral load. However, there is not a consensus on which sample type is the best for the test and what is its predictive value for therapeutic interventions.

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).

Therapy of chronic myeloid leukemia with imatinib mesylate in Brazil: a study of 98 cases / Tratamento da leucemia mielóide crônica com imatinib mesilato no Brasil: estudo de 98 casos

Chronic Myeloid Leukemia (CML) is a clonal disease characterized by balanced translocation between chromosomes 9 and 22 (Philadelphia chromosome). The resulting BCR-ABL gene has tyrosine kinase activity which stimulates cellular growth. Imatinib mesylate is a potent and specific inhibitor of all ABL related kinases. Ninety-eight CML patients were treated with imatinib mesylate from October 2000 to January 2003. Disease stage was: late chronic phase resistant or intolerant to alpha-interferon (CP): 28; accelerated phase (AP): 55; blastic phase (BP): 15 patients. Dose: 400 mg for CP and 600 mg for AP or CB. The objectives were to evaluation the efficacy, safety and survival with imatinib mesylate therapy in all phases of CML. The median follow up time was 545 days (range: 7-862), complete hematologic response was 86 percent in CP, 47 percent in AP and 13 percent in BP. Complete cytogenetic response was 61 percent, 24 percent and 0 percent respectively. BCR-ABL was not detected by nested RT-PCR in 9 percent of patients. Grade 3-4 hematologic toxicity was seen in 21 percent of CP, 74 percent of AP and 87 percent of BP patients. Grade 3-4 non-hematologic toxicity was observed in 11 percent of CP, 51 percent of AP and 53 percent of BP patients. Two-year overall survival was 64 percent for all patients, 96 percent for CP and 36 percent for AP patients. All BP patients died within a median of 60 days. Imatinib mesylate induced cytogenetic responses in Brazilian patients with previously treated CML in chronic and accelerated phase. Adverse events are similar to those reported in the literature, except for lower rates of gastrointestinal symptoms and muscle cramps in our study group.

INTRODUÇÃO: A Leucemia Mielóide Crônica (LMC) é uma doença clonal caracterizada pela presença da translocação entre os cromossomos 9 e 22 (cromossomo Philadelphia). O gene resultante BCR-ABL possui atividade de tirosino-quinase, que estimula o crescimento celular. O mesilato de imatinibe é um inibidor potente e específico de todas as quinases relacionadas ao ABL. PACIENTES E MÉTODOS: Noventa e oito pacientes com LMC foram tratados com mesilato de imatinibe de outubro de 2000 a janeiro de 2003: 28 em fase crônica (FC) resistente ou intolerante ao interferon alfa; 55 em fase acelerada (FA) e 55 em crise blástica (CB). Dose: 400 mg para CP e 600 mg para FA ou CB. OBJETIVOS: Avaliação da eficácia, segurança e sobrevida após tratamento da LMC com mesilato de imatinibe. RESULTADOS: Seguimento mediano: 545 dias (variação: 7-862). Resposta hematológica completa ocorreu em 86 por cento dos pacientes em FC, 47 por cento na FA e 13 por cento na CB. Sessenta e um por cento, 24 por cento e 0 por cento dos pacientes em FC, FA e CB, atingiram resposta citogenética completa, respectivamente. Não foram detectados transcritos BCR-ABL por "nested RT-PCR" em 9 por cento dos pacientes. Toxicidade hematológica grau 3-4: 21 por cento na FC, 74 por cento na FA e em 87 por cento na CB. Toxicidade não hematológica grau 3-4: 11 por cento na FC, 51 por cento na FA e 53 por cento na CB. A sobrevida global em dois anos foi de 64 por cento para todos os pacientes, 96 por cento na FC e 36 por cento na FA. Todos os pacientes em CB faleceram numa mediana de 60 dias. CONCLUSÕES: O mesilato de imatinibe induziu respostas citogenéticas completas em pacientes brasileiros com LMC em fase crônica e acelerada. Os eventos adversos nos nossos pacientes foram semelhantes aos relatados em literatura, exceto pela menor incidência de sintomas gastro-intestinais e câimbras.

Carcinoma de células escamosas em língua pós-transplante de medula óssea por Anemia de Fanconi / Squamous cell carcinoma of the tongue due to Fanconi's Anemia after bone marrow transplantation

Anemia Fanconi (AF) é uma síndrome autossômica recessiva, caracterizada por pancitopenia progressiva com hipoplasia de MO, em associação com várias anormalidades constitucionais, tendo como único recurso terapêutico com possibilidade potencial de cura o transplante de medula óssea, e sendo tais pacientes propensos ao desenvolvimento de malignidades hematológicas e carcinoma de células escamosas (CEC) em diversos locais: reto, vagina, cérvice, esôfago, cavidade bucal, faringe ou pele, mas especialmente em cabeça e pescoço. Relatamos aqui três casos de pacientes portadores de AF, que após TMO desenvolveram CEC em língua. Além disso, mencionamos fatores de risco relatados para tal evento, como diagnóstico de AF, condicionamento pré-transplante (quimioterápicos e irradiação), terapia com drogas imunossupressoras para tratamento de doença enxerto contra hospedeiro (DECH) aguda ou crônica, sexo e idade avançada. Além do que, discorremos sobre a existência de três mecanismos postulados que predispõem indivíduos com AF ao desenvolvimento de neoplasia: (1) defeito na reparação do DNA; (2) defeito na detoxificação de radicais de oxigênio; e (3) imunodeficiência.

Fanconi’s Anemia, first described in 1927, is a rareautonomic recessive disease characterized byprogressive pancytopenia, congenital malformations,spontaneous or chemically induced chromosomebreakage and increased incidence of leukemia andother cancers. The onset of bone marrow hypoplasiaand its hematological manifestations is usually in the3 - 7 year age range. Additionally, we discussed the existence ofthree postulated mechanisms that make individualswith Fanconi’s anemia susceptible to the developmentof neoplasias: (1) deficiency in the DNA repair system,(2) deficiency in oxygen radical detoxification; and(3) immunodeficiency.

Reversible posterior leucoencephalopathy syndrome associated with bone marrow transplantation

Reversible posterior leucoencephalopathy syndrome (RPLS) has previously been described in patients who have renal insufficiency, eclampsia, hypertensive encephalopathy and patients receiving immunosuppressive therapy. The mechanism by which immunosuppressive agents can cause this syndrome is not clear, but it is probably related with cytotoxic effects of these agents on the vascular endothelium. We report eight patients who received cyclosporine A (CSA) after allogeneic bone marrow transplantation or as treatment for severe aplastic anemia (SSA) who developed posterior leucoencephalopathy. The most common signs and symptoms were seizures and headache. Neurological dysfunction occurred preceded by or concomitant with high blood pressure and some degree of acute renal failure in six patients. Computerized tomography studies showed low-density white matter lesions involving the posterior areas of cerebral hemispheres. Symptoms and neuroimaging abnormalities were reversible and improvement occurred in all patients when given lower doses of CSA or when the drug was withdrawn. RPLS may be considered an expression of CSA neurotoxicity