The association between tumor EpsteinBarr virus (EBV) status and clinical outcome in Hodgkin lymphoma (HL) is controversial. This population-based study assessed the impact of EBV status on survival in age-stratified cohorts of adults with classic HL (cHL). Data from 437 cases were analyzed with a median follow-up of 93 months. Overall survival (OS) was significantly better for EBVnegative compared with EBV-positive patients (P < .001), with 5-year survival rates of 81% and 66%, respectively; diseasespecific survival (DSS) was also greater for EBV-negative patients (P ‫؍‬ .03). The impact of EBV status varied with age at diagnosis. In patients aged 16 to 34 years, EBV-associated cases had a survival advantage compared with EBV-negative cases, but differences were not statistically significant (P ‫؍‬ .21). Among patients 50 years or older, EBV positivity was associated with a significantly poorer outcome (P ‫؍‬ .

Summary. This study evaluated the incidence and outcome of Hodgkin's disease (HD) in older patients using a population-based approach. In total, 102 patients (52 men, 50 women) aged ‡ 60 years presented in the Northern Health Region of England (population of 3AE09 million) between 1 January 1991 and 31 December 1998 and were studied prospectively. The age-specific incidence was 1AE97/ 100 000 for those aged 60-69 years, and 2AE18/100 000 for those aged 70 years or over. The median age of the cohort was 70 years (range 60-91) and the median follow up was 63 months (range 20-113). Out of 95 treated patients, 70 (74%) obtained complete or good partial (> 90% response) remissions. In the 60 to 69-year-old group, the disease-specific survival at 5 years was 100% for those presenting with early stage disease and 52% for those with advanced stage disease. In patients aged >70 years the 5 year disease-specific survival was 36% in patients with early stage and 14% for patients with advanced stage disease. The survival of patients with Epstein-Barr virus (EBV)-positive tumours was significantly poorer than that of patients with EBV-negative tumours (P ¼ 0AE007); median survival in the former group was 20 months versus undefined in the latter group. In total, 43 deaths were due to progressive HD and five were treatment-related. This study defined the incidence of HD in our population and demonstrated that the prognosis of elderly patients, particularly those with advanced stage disease, has not improved concurrently with that of patients aged < 60 years old. Novel approaches to assessment and treatment are necessary.

After allogeneic stem cell transplantation, the establishment of the donor's immune system in an antigenically distinct recipient confers a therapeutic graft-versus-malignancy effect, but also causes graft-versus-host disease (GVHD) and protracted immune dysfunction. In the last decade, a molecular-level description of alloimmune interactions and the process of immune recovery leading to tolerance has emerged. Here, new developments in understanding alloresponses, genetic factors that modify them, and strategies to control immune reconstitution are described.In Section I, Dr. John Barrett and colleagues describe the cellular and molecular basis of the alloresponse and the mechanisms underlying the three major outcomes of engraftment, GVHD and the graft-versus-leukemia (GVL) effect. Increasing knowledge of leukemia-restricted antigens suggests ways to separate GVHD and GVL. T cellsThe alloresponse segregates into induction, expansion, and effector phases. In the induction phase, donor CD8 and CD4 T cells interact with peptide antigens complexed with major histocompatibility complex (MHC) class I and II molecules, respectively, on antigen-presenting cells (APCs) of the recipient. The signal given by the MHC through the T-cell receptor (TCR) and CD3, CD4, or CD8 provides the first signal for Tcell activation. A full T-cell response, leading to proliferation of effector cells, requires a second signal delivered by interaction by costimulatory molecules such as CD80 and CD86 on the APCs and CD28 on the lymphocyte surface. During the expansion phase, T cells proliferate, particularly under the influence of growth factors interleukin (IL)-2 and IL-12. The milieu in which T cells expand determines whether they assume the characteristics of T helper (Th) or T cytotoxic (Tc) type 1, or Th/Tc type 2 cells, which have distinct proor antiinflammatory functional properties, respectively.

Because sTNFRIIs can act as TNF antagonists, the association between recipient and donor TNFRII 196R allele status and acute or extensive chronic GVHD incidence, respectively, may reflect reduced circulating sTNFRII.

Graft-vs-host disease (GVHD) remains a key limiting factor in the success of hematopoietic stem cell transplantation (HSCT). One of the key cytokines known to have a role in the pathogenesis of GVHD is interleukin-1 (IL-1). The IL-1 gene family consists of 10 members, of which 3 genes encode for the proteins IL-1a, IL-1ss and IL-1Ra (IL-1 receptor antagonist). Polymorphisms in these genes have been associated with variability in the production of the respective cytokines and have been implicated in patient susceptibility to inflammatory diseases, including GVHD. A number of reports have detailed genetic associations between members of the IL-1 gene family and HSCT outcomes. Despite these encouraging reports, a simple exploitation of these findings is probably naive. Differences in transplant practice between centers and within centers over time mean that directly comparable studies are rare. This combined with the complexity of IL-1-related transplant biology means that our understanding of this topic remains limited. This review details the current state of knowledge of IL-1 genetics and transplantation and discusses these issues in the context of the changing practice of transplantation.