Impact of cytomegalovirus and grafts versus host disease on the dynamics of CD57+CD28-CD8+ T cells after bone marrow transplant

OBJECTIVES: The present study aimed to evaluate the dynamics of CD28 and CD57 expression in CD8+ T lymphocytes during cytomegalovirus viremia in bone marrow transplant recipients. METHODS: In a prospective study, blood samples were obtained once weekly once from 33 healthy volunteers and weekly from 33 patients. To evaluate the expression of CD57 and CD28 on CD8+ T lymphocytes, flow cytometry analysis was performed on blood samples for four months after bone marrow transplant, together with cytomegalovirus antigenemia assays. RESULTS: Compared to cytomegalovirus-seronegative healthy subjects, seropositive healthy subjects demonstrated a higher percentage of CD57+ and a lower percentage of CD28+ cells (p<0.05). A linear regression model demonstrated a continuous decrease in CD28+ expression and a continuous increase in CD57+ expression after bone marrow transplant. The occurrence of cytomegalovirus antigenemia was associated with a steep drop in the percentage of CD28+ cells (5.94 percent, p<0.01) and an increase in CD57+ lymphocytes (5.60 percent, p<0.01). This cytomegalovirus-dependent effect was for the most part concentrated in the allogeneic bone marrow transplant patients. The development of acute graft versus host disease, which occurred at an earlier time than antigenemia (day 26 vs. day 56 post- bone marrow transplant), also had an impact on the CD57+ subset, triggering an increase of 4.9 percent in CD57+ lymphocytes (p<0.05). CONCLUSION: We found continuous relative changes in the CD28+ and CD57+ subsets during the first 120 days post- bone marrow transplant, as part of immune system reconstitution and maturation. A clear correlation was observed between the expansion of the CD57+CD28-CD8+ T lymphocyte subpopulation and the occurrence of graft versus host disease and cytomegalovirus viremia.

Novas diretrizes na abordagem clínica da neutropenia febril e da sepse em oncologia pediátrica / New guidelines for the clinical management of febrile neutropenia and sepsis in pediatric oncology patients

OBJETIVOS: Fornecer subsídios à abordagem diagnóstica, profilática e terapêutica da neutropenia febril e da sepse em criança com doença oncológica, dando especial atenção aos novos protocolos e diretrizes. FONTES DE DADOS: Revisão de literatura científica utilizando uma busca bibliográfica eletrônica nas páginas do MEDLINE, Medscape, SciELO, Google, Cochrane e PubMED com as palavras-chave febrile, neutropenic, cancer, children, sepse, intensive, care. Foram selecionados artigos publicados entre 1987 e 2007, preferencialmente artigos de revisão, protocolos, revisões sistemáticas, estudos epidemiológicos, recomendações de força-tarefa e ensaios clínicos fase III. Foram revistos os consensos publicados pela Infectious Diseases Society of America, Center for Diseases Control e Infectious Diseases Working Party da German Society of Hematology and Oncology, além de recomendações da World Federation of Pediatric Intensive and Critical Care Societies e da Society of Critical Care Medicine. SíNTESE DOS DADOS: A utilização de esquemas quimioterápicos agressivos, transplante de medula óssea e recursos de terapia intensiva aumentaram a sobrevida nas crianças com câncer e também a morbidade infecciosa, sendo as complicações sépticas a principal causa de mortalidade. Diversos fatores de risco têm sido identificados, como neutropenia, tipo oncológico, sinais clínicos e marcadores de resposta inflamatória (reação em cadeia da polimerase, procalcitonina), assim como a maior resistência aos antimicrobianos e antifúngicos. Protocolos de classificação de risco, de diagnóstico e tratamento devem ser estabelecidos em cada serviço, respeitando a flora microbiológica da população estudada. A terapia intensiva pediátrica tem aumentado a sobrevida a curto e longo prazo nestes pacientes. CONCLUSÕES: Pacientes oncológicos são particularmente vulneráveis a complicações infecciosas. A identificação e o tratamento precoce são fundamentais para a melhora da sobrevida.

OBJECTIVES: To provide a foundation for the diagnostic, prophylactic and therapeutic management of febrile neutropenia and sepsis in children with oncological diseases, with special attention to new protocols and guidelines. SOURCES: A review of the scientific literature utilizing an electronic bibliographic search on MEDLINE, Medscape, SciELO, Google, Cochrane and PubMED using the keywords febrile, neutropenic, cancer, children, sepsis, intensive, care. Articles published between 1987 and 2007 were selected, with preference given to review articles, protocols, systematic reviews, epidemiological studies, task force recommendations and phase III clinical trials. Consensus documents published by the Infectious Diseases Society of America, the Center for Diseases Control and the Infectious Diseases Working Party of the German Society of Hematology and Oncology, in addition to the recommendations of the World Federation of Pediatric Intensive and Critical Care Societies and Society of Critical Care Medicine, were also reviewed. SUMMARY OF THE FINDINGS: The use of aggressive chemotherapy regimens, bone marrow transplantation and intensive care resources have increased the survival rates of children with cancer and also their infectious morbidity, with septic complications as the principal cause of mortality. Several risk factors have been identified, such as neutropenia, oncology type, clinical signs and inflammatory response markers (polymerase chain reaction, procalcitonin) and also increased resistance to antimicrobials and antifungal agents. Protocols for risk classification, diagnosis and treatment should be established at each service, taking into account the microbiological flora of each population. Pediatric intensive care has increased the short and long-term survival of these patients. CONCLUSIONS: Oncology patients are particularly vulnerable to infectious complications. Early identification and treatment are fundamental to improving...