Chronic graft-versus-host disease : a risk factor for secondary malignancies after allogeneic stem-cell transplant

Trabalho Final do Curso de Mestrado Integrado em Medicina, Faculdade de Medicina, Universidade de Lisboa, 2018Enquadramento: Apesar dos avanços na área da transplantação de células progenitoras hematopoiéticas, o transplante alogénico continua a associar-se a importantes complicações, com elevada morbi-mortalidade, como a doença de enxerto-contrahospedeiro crónica e neoplasias secundárias. A doença de enxerto-contra-hospedeiro crónica e o seu tratamento foram identificados como potenciais factores de risco para o desenvolvimento de neoplasias secundárias após transplante, nomeadamente neoplasias sólidas. No entanto existem poucos estudos que analisem o papel da doença de enxertocontra- hospedeiro crónica no risco de neoplasias secundárias. Objectivo: Analisar e clarificar o papel da doença de enxerto-contra-hospedeiro crónica e do tratamento imunosupressor associado, no desenvolvimento de neoplasias secundárias após transplante alogénico de células progenitoras hematopoieticas. Como objectivo final, este trabalho pretende aumentar a sensibilização para esta complicação tardia, no seguimento a longo-prazo destes doentes. Método: Revisão sistemática da literatura, através da pesquisa na base de dados Pubmed, com inclusão final de 29 artigos científicos. Resultados: A doença de enxerto-contra-hospedeiro crónica parece ser um factor de risco independente para neoplasias sólidas, nomeadamente para carcinomas pavimentocelulares de regiões frequentemente afectadas pela doença, como a cavidade oral, pele e, nalgumas populações, o esófago. O risco de neoplasia sólida parece aumentar com a duração do tratamento imunosupressor, quando este é superior a 24 meses, e com o uso de azatioprina. A associação da doença de enxerto-contra-hospedeiro crónica com outros tipos de neoplasias secundárias foi inconclusiva. Conclusão: Os doentes com doença de enxerto-contra-hospedeiro crónica parecem ter um risco aumentado para neoplasias secundárias, nomeadamente neoplasias sólidas. Estas neoplasias tendem a surgir tardiamente, o que sugere um benefício na instituição de rotinas de rastreio oncológico a longo-termo, sobretudo para neoplasias da pele, cavidade oral, e nalgumas populações, esófago.Background: Despite the advances in hematopoietic stem cell transplantation, allogeneic transplants are still associated with significant morbidity and mortality, due to late complications, such as chronic graft-versus-host disease and secondary malignancies. Both chronic graft-versus-host disease and its treatment have been implied as potential risk factors for secondary malignancies in patients undergoing allogeneic hematopoietic stem cell transplant, particularly for solid tumors. However the literature on the role of chronic graft-versus-host disease on the development of secondary malignancy is scarce. Goals: Analyze and clarify the role of chronic graft-versus-host disease, and its immunosuppressive treatment, on the development of secondary malignancies after allogeneic stem cell transplantation. The final goal is to increase awareness for this late complication in the long-term follow up of these patients. Methods: This is a systematic literature review, covering 29 articles, after a thorough search in Pubmed database. Results: Chronic graft-versus-host disease seems to be an independent risk factor for solid tumors, namely for squamous cell carcinomas of regions frequently affected by the disease, such as the oral cavity, skin and, in some populations, the esophagus. The risk for solid tumors seems to increase with treatment duration, when surpassing 24 months, and with the use of azathioprine. The association between chronic graft-versus-host disease and other secondary malignancies was inconclusive. Conclusions: Patients with chronic graft-versus-host disease seem to have an increased risk for secondary malignancies, namely solid tumors. Solid tumors tend to occur later in the follow-up, suggesting a benefit in cancer screening guidelines for the long-termsurvivors, particularly for skin, oral cavity, and esophagus cancer

Characterisation of microbial attack on archaeological bone

As part of an EU funded project to investigate the factors influencing bone preservation in the archaeological record, more than 250 bones from 41 archaeological sites in five countries spanning four climatic regions were studied for diagenetic alteration. Sites were selected to cover a range of environmental conditions and archaeological contexts. Microscopic and physical (mercury intrusion porosimetry) analyses of these bones revealed that the majority (68%) had suffered microbial attack. Furthermore, significant differences were found between animal and human bone in both the state of preservation and the type of microbial attack present. These differences in preservation might result from differences in early taphonomy of the bones. © 2003 Elsevier Science Ltd. All rights reserved