Background: Few studies have investigated the relationship between physician and patient-assessed performance status (PS) in blood cancers. Methods: Retrospective analysis among 1418 patients with haematologic malignancies seen at Dana-Farber Cancer Institute between 2007 and 2014. We analysed physician-patient agreement of Eastern Cooperative Oncology Group PS using weighted kappa-statistics and survival analysis. Results: Mean age was 58.6 years and average follow-up was 38 months. Agreement in PS was fair/moderate (weighted kappa = 0.41, 95% CI 0.37-0.44). Physicians assigned a better functional status (lower score) than patients (mean 0.60 vs 0.81), particularly when patients were young and the disease was aggressive. Both scores independently predicted survival, but physician scores were more accurate. Disagreements in score were associated with poorer survival when physicians rated PS better than patients, and were modified by age, sex and severity of disease. Conclusions: Physician-patient disagreements in PS score are common and have prognostic significance.

Made available in DSpace on 2014-08-20T14:37:52Z (GMT). No. of bitstreams: 1 tese_regina_reiniger.pdf: 944227 bytes, checksum: 66a993c5dfb5442061261f6e6b57216a (MD5) Previous issue date: 2012-12-21 / The aim of this study was to evaluate the effect of the transfer of passive immunity and pathophysiological effects against experimental Haemonchus placei or H. contortus primary infection and challenge. The first experiment evaluated the transmission of passive immunity in parasite-free lambs. At 6-month old, lambs were divided in three groups: infected with H. contortus (Hc), with H. placei (Hp) and uninfected (C for control), and challenged at 9-month old when lambs were again divided in four groups: Hc-Hc, Hc-Hp, Hp-Hc and C-C. Serological analyses showed the transfer of anti-H. contortus IgG, but with a gradual decline over time in both females and lambs. During primary infection, faecal egg count (FEC) average was twice for the Hc group compared to Hp (p <0.0001). The Hc group presented the lowest packed cell volume compared to the other groups (p <0.0001). Primo-infected sheep with either H. placei or H. contortus did not develop resistance when challenged with same species- or across-species parasite. Single 5,000 L3 dose experimental infection was not sufficient to cause clinical signs, nor to rise and maintain anti-H. contortus IgG levels in the infected animals. There is passive transfer of anti-H. contortus IgG for lambs through the colostrum, however the IgG levels begin a gradual decrease from day 30 after birth. / O objetivo deste estudo foi avaliar o efeito da transmissão da imunidade passiva e efeitos fisiopatológicos frente à infecção experimental primária e desafio de cordeiros com Haemonchus placei ou H. contortus. Na primeira fase experimental avaliou-se a transmissão da imunidade passiva em cordeiros, mantidos livres de infecções por nematódeos gastrintestinais. Posteriormente cordeiros com seis meses de idade, divididos em três grupos: infectados com H. contortus (Hc), com H. placei (Hp) e não infectados (C). E para o desafio os cordeiros foram divididos quatro grupos: Hc-Hc, Hc-Hp, Hp-Hc e C-C. As análises sorológicas evidenciaram a transferência de anticorpos IgG anti-H. contortus, porém com um declínio gradual ao longo do tempo tanto nas fêmeas como cordeiros. Durante a primo-infecção a média de OPG do grupo Hc foi duas vezes superior ao grupo Hp (p<0,0001). O grupo Hc apresentou as menores médias de volume globular, em relação aos demais grupos (p<0,0001). Os animais primo infectados, tanto com H. placei como H. contortus, não desenvolveram resistência quando desafiados, tanto com a mesma espécie ou cruzada de Haemonchus. A infecção experimental em única dose de 5000 L3 não foi suficiente para provocar sinais clínicos, elevar e manter os níveis de IgG anti-H. contortus nos animais infectados. Há transmissão passiva de IgG anti-H. contortus para os cordeiros através do colostro, entretanto estes iniciam uma queda gradativa já a partir do 30º dia pós nascimento.

Graft-versus-host disease (GvHD) remains one of the major complications following allogeneic haematopoietic stem cell transplantation (allo-HSCT). GvHD can occur in almost every tissue, with the skin, liver, and intestines being the mainly affected organs. T cells are implicated in initiating GvHD. T cells identify a broad range of antigens and mediate the immune response through receptors on their surfaces (T cell receptors, TCRs). The composition of TCRs within a T cell population defines the TCR repertoire of an individual, and this repertoire represents exposure to self and non-self proteins. Monitoring the changes in the TCR repertoire using TCR sequencing can provide an indication of the dynamics of a T cell population. Monitoring the frequency and specificities of specific TCR clonotypes longitudinally in different conditions and specimens (peripheral blood, GvHD-affected tissue samples) can provide insights into factors modulating immune reactions following allogeneic transplantation and will help to understand the underlying mechanisms mediating GvHD. This review provides insights into current studies of the TCR repertoire in GvHD and potential future clinical implications of TCR sequencing.